Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Prognostic Significance of MicroRNA-375 Downregulation in Solid Tumors: A Meta-Analysis Thu, 23 Oct 2014 07:56:36 +0000 http://www.hindawi.com/journals/dm/2014/626185/ Objective. Recently, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may play an important role as prognostic biomarker of cancers. We performed a meta-analysis to evaluate the impact of miR-375 expression in solid tumors on patients’ overall survival (OS). Methods. Studies were identified by searching PubMed, Embace, and Cochrane Library (last search update was in May 2014) and were assessed by further quality evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for total and stratified analyses were calculated to investigate the association between miR-375 expression and cancer patients OS. Results. Our analysis results indicated that downregulation of miR-375 predicted poor OS (HR = 1.91, 95% CI 1.48–2.45, ). Subgroup analyses showed that lower expression of miR-375 was significantly related with poor OS in patients with esophageal carcinoma (HR = 2.24, 95% CI 1.69–2.96, ) and non-small-cell lung cancer (NSCLC) (HR = 1.71, 95% CI 1.31–2.24, ). Conclusions. The findings from this meta-analysis suggest that miR-375 expression is associated with OS of patients with malignant tumors and could be a useful clinical prognostic biomarker. Yingjie Shao, Yiting Geng, Wendong Gu, Jin Huang, Zhonghua Ning, and Honglei Pei Copyright © 2014 Yingjie Shao et al. All rights reserved. MicroRNA-21 Promotes Cell Growth and Migration by Targeting Programmed Cell Death 4 Gene in Kazakh’s Esophageal Squamous Cell Carcinoma Tue, 21 Oct 2014 12:02:18 +0000 http://www.hindawi.com/journals/dm/2014/232837/ Esophageal cancer (EC) is the eighth most common cancer worldwide and the sixth most common cause of cancer death. There are two main types of EC—squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). Although some advances in the exploration of its possible etiological mechanism were made recently including behaviors and environmental risk factors as well as gene alterations, the molecular mechanism underlying ESCC carcinogenesis and progression remains poorly understood. It has been reported that miR-21 was upregulated in most malignant cancers, the proposed mechanism of which was through suppressing expression of programmed cell death 4 (PDCD4). In present study, it is firstly reported that miR-21 was upregulated in Kazakh’s ESCC and that miR-21 played a negative role in regulating PDCD4 using in situ hybridization (ISH) and luciferase reporter approach. Morever, in model of ESCC xenografted nude mice, miR-21 maybe used as an effective target in the treatment. The present results demonstrated that miR-21 may be a potential therapeutic target in management of ESCC. Tao Liu, Qing Liu, Shutao Zheng, Xiangpeng Gao, Mang Lu, Chenchen Yang, Fang Dai, Ilyar Sheyhidin, and Xiaomei Lu Copyright © 2014 Tao Liu et al. All rights reserved. The Association between Bile Salt Export Pump Single-Nucleotide Polymorphisms and Primary Biliary Cirrhosis Susceptibility and Ursodeoxycholic Acid Response Sun, 19 Oct 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/350690/ Background. Primary biliary cirrhosis (PBC) is a chronic and progressive cholestasis liver disease. Bile salt export pump (BSEP) is the predominant bile salt efflux system of hepatocytes. BSEP gene has been attached great importance in the susceptibility of PBC and the response rate of ursodeoxycholic acid (UDCA) treatment of PBC patients. Methods. In this study, TaqMan assay was used to genotype four variants of BSEP, and the Barcelona criteria were used for evaluating the response rate of UDCA treatment. Results. Variant A allele of BSEP rs473351 (dominant model, OR = 2.063; 95% CI, 1.254–3.393; ) was highly associated with PBC susceptibility. On the contrary, variant A allele of BSEP rs2287618 (dominant model, OR = 0.617; 95% CI, 0.411–0.928; ) provided a protective role and Barcelona evaluation criterion indicated that the frequency of variant allele at BSEP rs2287618 was significantly decreased in UDCA-responsive PBC patients (). Conclusion. These results suggested that BSEP rs473351 was closely associated with the susceptibility of PBC and if people with BSEP rs2287618 were diagnosed as PBC, the UDCA treatment was not satisfactory. Larger studies with mixed ethnicity subjects and stratified by clinical and subclinical characteristics are needed to validate our findings. Rui-rui Chen, Yuan-jun Li, Xin-min Zhou, Lu Wang, Juan Xing, Shuang Han, Li-na Cui, Lin-hua Zheng, Kai-chun Wu, Yong-quan Shi, Zhe-yi Han, Ying Han, and Dai-ming Fan Copyright © 2014 Rui-rui Chen et al. All rights reserved. Prediabetes Is Associated with HNF-4α P2 Promoter Polymorphism rs1884613: A Case-Control Study in Han Chinese Population and an Updated Meta-Analysis Wed, 15 Oct 2014 11:28:55 +0000 http://www.hindawi.com/journals/dm/2014/231736/ Background. Controversy remains for the association between hepatocyte nuclear factor 4α (HNF-4α) P2 promoter polymorphism rs1884613 and type 2 diabetes (T2D). There was no association test of this polymorphism with prediabetes and T2D in the Chinese population. Moreover, an updated meta-analysis in various ethnic groups is needed to establish the contribution of rs1884613 to T2D risk. Methods. Using the Sequenom MassARRAY platform approach, we genotyped rs1884613 of HNF-4α in the P2 promoter region among 490 T2D patients, 471 individuals with prediabetes, and 575 healthy controls. All the individuals were recruited from 16 community health service centers in Nanshan district in Shenzhen province. Using STATA 11.0 software, meta-analysis was performed to summarize the overall contribution of rs1884613 to T2D risk. Results. Polymorphism rs1884613 was associated with genetic susceptibility to prediabetes in the whole samples (OR = 1.40, 95% CI = 1.16–1.68, ) and the female subgrouped samples (OR = 1.48, 95% CI = 1.14–1.92, ) after adjusting for age and body mass index (BMI). In contrast, there was no association of rs1884613 with T2D in the whole samples and male in our case-control study and meta-analysis. Conclusions. Our results suggest that rs1884613 contributes to susceptibility to prediabetes, whereas this polymorphism may not play an important role in the development of T2D. Changyi Wang, Sihan Chen, Tao Zhang, Zhongwei Chen, Shengyuan Liu, Xiaolin Peng, Jianping Ma, Xiaohong Zhong, Yanqiong Yan, Linlin Tang, Yifeng Mai, Liyuan Han, and Shiwei Duan Copyright © 2014 Changyi Wang et al. All rights reserved. Hepatocyte Growth Factor Levels in the Saliva and Gingival Crevicular Fluid in Smokers with Periodontitis Wed, 15 Oct 2014 08:25:48 +0000 http://www.hindawi.com/journals/dm/2014/146974/ Hepatocyte growth factor (HGF) production by oral fibroblasts is enhanced by various molecules that are induced during inflammatory conditions including periodontitis. HGF plays an important role in the progression of periodontitis, by stimulating intense growth of epithelial cells and preventing regeneration of connective tissue attachments. Smokers have a greater risk factor in the pathogenesis and progression of periodontal disease. The objective of the study was to estimate the level of HGF in saliva and gingival crevicular fluid (GCF) in smokers with periodontitis and to compare these levels with that of nonsmokers with periodontitis and healthy controls. The HGF levels were found to be significantly high in the saliva and GCF of smokers with periodontitis compared to both never-smokers with periodontitis and the healthy control group. The elevated levels of HGF in the saliva and GCF in the study population could explain the intrinsic mechanism triggering the severity of the periodontitis in smokers. Further studies are necessary to validate the current observations and to establish a sensitive marker to predict periodontal disease activity. Sukumaran Anil, Sajith Vellappally, R. S. Preethanath, Sameer A. Mokeem, Hani S. AlMoharib, Shankargouda Patil, Elna P. Chalisserry, and Abdulaziz A. Al Kheraif Copyright © 2014 Sukumaran Anil et al. All rights reserved. Can Serum Glypican-3 Be a Biomarker for Effective Diagnosis of Hepatocellular Carcinoma? A Meta-Analysis of the Literature Tue, 14 Oct 2014 12:43:01 +0000 http://www.hindawi.com/journals/dm/2014/127831/ Objective. This review is to evaluate the diagnostic value of serum GPC3 for hepatocellular carcinoma (HCC) due to conflicting results reported. Methods. NCBI PubMed and Embase were comprehensively searched for studies that have used serum GPC3 level as a diagnostic index for HCC. The quality of the included studies was assessed. Subgroup analyses were conducted to evaluate the sensitivity and specificity of GPC3 as a HCC marker. Statistical analysis was performed with the software STATA version 12.0. Results. A total of 22 studies were included. The qualities of included studies were relatively poor. Among them, 18 studies have shown that serum GPC3 is a specific biomarker for HCC, and the pooled sensitivity and specificity of these studies were 69 and 93%, respectively. The other 4 studies have reported conflicting results, which were not caused by races, infection status of HBV and HCV, or assay reagents but due to one common experimental design of enrolling liver cirrhosis patients as control subjects. Conclusions. This meta-analysis indicates that serum GPC3 is elevated in HCC patients compared with healthy individuals, but more studies are needed to evaluate its effectiveness to differentially diagnose HCC and liver cirrhosis. Sheng-Li Yang, Xiefan Fang, Zao-Zao Huang, Xiang-Jie Liu, Zhi-Fan Xiong, Ping Liu, Hong-Yi Yao, and Chang-Hai Li Copyright © 2014 Sheng-Li Yang et al. All rights reserved. Prognostic Value of Rab27B Nuclear Expression in Gastrointestinal Stromal Tumors Tue, 14 Oct 2014 07:10:08 +0000 http://www.hindawi.com/journals/dm/2014/942181/ Rab proteins of the endocytosis and exocytosis pathways both play critical roles in cancer progression, and Rab27B has a significant relationship with several types of human cancer. However, the association between Rab27B expression and clinical features to determine its clinicopathological significance in gastrointestinal tumor (GIST) has not been investigated. To examine the expression of Rab27B in GIST and investigate the association between its expression and patient prognosis, immunohistochemistry analysis with tissue microarray was used to evaluate expression of Rab27B in 162 patients with GIST. The relationship between Rab27B expression and patient prognosis was analyzed. High nuclear staining of Rab27B was detected in 88 of 162 (54.32%) GIST tissues. Positive staining of Rab27B was significantly associated with tumor size (), mitotic index (), Armed Forces Institute of Pathology Miettinen risk classification (), and tumor grade (). Kaplan-Meier survival curves showed that GIST patients with low Rab27B nuclear expression () and mitotic index <5 per 50 high-power fields () had a more favorable prognosis. These findings indicate that Rab27B nuclear expression is correlated with several clinicopathological features of GIST patients, and it may serve as an unfavorable prognostic marker. Wei Wang, Qichao Ni, Hua Wang, Shu Zhang, and Huijun Zhu Copyright © 2014 Wei Wang et al. All rights reserved. Individually Tailored Screening of Susceptibility to Sarcopenia Using p53 Codon 72 Polymorphism, Phenotypes, and Conventional Risk Factors Mon, 13 Oct 2014 13:20:26 +0000 http://www.hindawi.com/journals/dm/2014/743634/ Background and Aim. p53 activity plays a role in muscle homeostasis and skeletal muscle differentiation; all pathways that lead to sarcopenia are related to p53 activities. We investigate the allelic frequency of the TP53 codon 72 in exon 4 polymorphism in the Italian female population and the association with appendicular skeletal muscle mass index in normal weight (NW), normal weight obese (NWO), and preobese-obese (Preob-Ob) subjects. Methods. We evaluated anthropometry, body composition, and p53 polymorphism in 140 women distinguished in NW, NWO, and Preob-Ob. Results. (RR = 0,31, 95% CI = 0,15–0,66, P = 0,0079). We developed a model able to predict sarcopenia risk based on age, body fat, and p53 polymorphism. Conclusion. Our study evidences that genotyping TP53 polymorphism could be a useful new genetic approach, in association with body composition evaluations, to assess sarcopenia risk. Laura Di Renzo, Santo Gratteri, Francesca Sarlo, Andrea Cabibbo, Carmen Colica, and Antonino De Lorenzo Copyright © 2014 Laura Di Renzo et al. All rights reserved. Importance of Follow-Up Cerebrospinal Fluid Analysis in Cryptococcal Meningoencephalitis Mon, 13 Oct 2014 12:07:39 +0000 http://www.hindawi.com/journals/dm/2014/162576/ Cryptococcal meningoencephalitis represents a serious infection of the central nervous system, where reliable prognostic factors during the disease course are needed. Twenty-one patients diagnosed with cryptococcal meningoencephalitis in a German university hospital from 1999 to 2013 were analysed retrospectively. CSF parameters were analysed prior to therapy and during antifungal treatment and were compared between patients who survived or deceased. Fifteen patients clinically improved after antifungal therapy, while six patients died. No differences were observed between the outcome groups for the CSF parameters cell count, lactate, total protein, and CSF-serum albumin quotients (QAlb). Follow-up examinations of serum cryptococcal antigen titer and CSF cell count have shown that these parameters cannot be used to monitor the efficacy of antifungal therapy as well. In contrast, the course of QAlb during therapy was indicative for the outcome as a possible prognostic marker. In patients with clinical improvement QAlb values were falling under therapy, while rising QAlb values were found in patients with fatal outcome indicating a continuing dysfunction of the blood-CSF barrier. In conclusion, our results indicate that, among the various CSF parameters, the course of QAlb presents a promising marker that might be used to monitor the efficacy of antifungal therapy. Thomas Skripuletz, Philipp Schwenkenbecher, Kaweh Pars, Matthias Stoll, Josef Conzen, Seza Bolat, Refik Pul, Ralf-Peter Vonberg, Ludwig Sedlacek, Ulrich Wurster, Martin Stangel, and Corinna Trebst Copyright © 2014 Thomas Skripuletz et al. All rights reserved. Elevated Plasma Stromal-Cell-Derived Factor-1 Protein Levels Correlate with Severity in Patients with Community-Acquired Pneumonia Mon, 13 Oct 2014 09:21:48 +0000 http://www.hindawi.com/journals/dm/2014/829706/ Background. The aim of this study was to investigate differential changes in plasma levels of stromal-cell-derived factor-1 (SDF-1) before and after antibiotic treatment in patients with community-acquired pneumonia (CAP) and observe the association between the severity of CAP and the plasma SDF-1 level. Methods. We gathered blood specimens from 61 adult CAP patients before and after antibiotic treatment and from 60 healthy controls to measure the plasma concentrations of SDF-1 by using an enzyme-linked immunosorbent assay. Results. The plasma SDF-1 concentration was elevated significantly in patients with CAP before receiving treatment compared with the controls and decreased significantly after the patients received treatment. Leukocyte (WBC) and neutrophil counts and C-reactive protein (CRP) levels decreased significantly after antibiotic treatment. Moreover, differences in the plasma concentration of SDF-1 were significantly correlated with PSI, CURB-65, and APACHE II scores (, , and ; , , and ; and , , and , resp.). Conclusions. An elevated plasma SDF-1 concentration can be used as a biological marker for the early diagnosis of CAP and for the early detection of its severity. Ping-Kun Tsai, Ming-Ju Hsieh, Hsiang-Ling Wang, Ming-Chih Chou, Shun-Fa Yang, and Chao-Bin Yeh Copyright © 2014 Ping-Kun Tsai et al. All rights reserved. System Accuracy Evaluation of the GlucoRx Nexus Voice TD-4280 Blood Glucose Monitoring System Mon, 13 Oct 2014 07:30:26 +0000 http://www.hindawi.com/journals/dm/2014/602586/ Use of blood glucose (BG) meters in the self-monitoring of blood glucose (SMBG) significantly lowers the risk of diabetic complications. With several BG meters now commercially available, the International Organization for Standardization (ISO) ensures that each BG meter conforms to a set degree of accuracy. Although adherence to ISO guidelines is a prerequisite for commercialization in Europe, several BG meters claim to meet the ISO guidelines yet fail to do so on internal validation. We conducted a study to determine whether the accuracy of the GlucoRx Nexus TD-4280 meter, utilized by our department for its cost-effectiveness, complied with ISO guidelines. 105 patients requiring laboratory blood glucose analysis were randomly selected and reference measurements were determined by the UniCel DxC 800 clinical system. Overall the BG meter failed to adhere to the ≥95% accuracy criterion required by both the 15197:2003 (overall accuracy 92.4%) and 15197:2013 protocol (overall accuracy 86.7%). Inaccurate meters have an inherent risk of over- and/or underestimating the true BG concentration, thereby risking patients to incorrect therapeutic interventions. Our study demonstrates the importance of internally validating the accuracy of BG meters to ensure that its accuracy is accepted by standardized guidelines. Muhammad Khan, Keith Broadbent, Mike Morris, David Ewins, and Franklin Joseph Copyright © 2014 Muhammad Khan et al. All rights reserved. A Comparison of KL-6 and Clara Cell Protein as Markers for Predicting Bronchopulmonary Dysplasia in Preterm Infants Wed, 27 Aug 2014 11:53:19 +0000 http://www.hindawi.com/journals/dm/2014/736536/ Objectives. To evaluate the predictive characteristics of KL-6 and CC16 for bronchopulmonary dysplasia (BPD) in preterm infants, either independently or in combination. Study Design. This prospective cohort study was performed from 2011 to 2013 with preterm neonates of gestational age ≤32 weeks and birth weight ≤1500 g. Serum KL-6 and CC16 levels were determined 7 and 14 days after birth. Results. Seventy-three preterm infants were studied. BPD was identified in 24 of these infants. After adjusting for potential confounders, serum KL-6 concentrations were found to be elevated in BPD infants at both time points relative to non-BPD infants, while serum CC16 concentrations were lower at 14 days. At both 7 d and 14 d of life the predictive power of KL-6 levels exceeded that of CC16 (area under receiver operating characteristic curve: at 7 d, 0.91 cf. 0.73, ; at 14 d, 0.95 cf. 0.85, ). The combination of these markers enhanced the sensitivity further. Conclusions. Serum KL-6 levels higher than 79.26 ng/mL at 14 days postpartum in preterm infants predict the occurrence of BPD. CC16 was less predictive than KL-6 at this time point, but KL-6 and CC16 together enhanced the prediction. Keyi Wang, Xianmei Huang, Hui Lu, and Zhiqun Zhang Copyright © 2014 Keyi Wang et al. All rights reserved. Two Polymorphisms in the Fractalkine Receptor CX3CR1 Gene Influence the Development of Atherosclerosis: A Meta-Analysis Tue, 26 Aug 2014 06:08:28 +0000 http://www.hindawi.com/journals/dm/2014/913678/ Background. The associations between the Fractalkine receptor (CX3CR1) gene T280M (rs3732378) and V249I (rs3732379) polymorphisms and atherosclerosis (AS) risk are conflicting. The aim of this meta-analysis was undertaken to assess their associations. Methods. PubMed, Embase, Web of Science, Medline, Cochrane database, and CNKI were searched to get the genetic association studies. All statistical analyses were done with Stata 11.0. Results. Twenty-five articles involving 49 studies were included in the final meta-analysis. The analysis showed that the 280M allele carriers of the CX3CR1 T280M polymorphism decreased the risk of AS and coronary artery disease (CAD) in the heterozygous state but increased the risk of ischemic cerebrovascular disease (ICVD) in the homozygote state. The 249I allele carriers of the CX3CR1 V249I polymorphism decreased the risk of AS and CAD in the heterozygous state. The V249I-T280M combined genotype VITM and IITM also decreased the risk of AS. Conclusions. The present meta-analysis suggests that the CX3CR1 T280M and V249I polymorphisms are associated with the susceptibility to AS. However, the results should be interpreted with caution because of the high heterogeneity in the meta-analysis. Jian Wu, Rui-Xing Yin, Quan-Zhen Lin, Tao Guo, Guang-Yuan Shi, Jia-Qi Sun, Shao-Wen Shen, and Qing Li Copyright © 2014 Jian Wu et al. All rights reserved. Lead Exposure: A Summary of Global Studies and the Need for New Studies from Saudi Arabia Tue, 19 Aug 2014 06:09:49 +0000 http://www.hindawi.com/journals/dm/2014/415160/ Lead poisoning (plumbism) can cause irreversible genetic and reproductive toxicity, hematological effects, neurological damage, and cardiovascular effects. Despite many efforts to minimize lead poisoning, it continues to be a major health concern in many developing and developed countries. Despite efforts to control lead exposure and toxicity, serious cases of lead poisoning increasingly occur as a result of higher vehicular traffic and industrialization. The biomarkers for identification of genetic susceptibility to a particular disease are useful to identify individuals who are at risk for lead poisoning. Although many such studies have been taken up elsewhere, very few studies were performed in Saudi Arabia to assess susceptibility to lead poisoning. This indicates an urgent need for testing of susceptible individuals. The present paper was planned to understand the genetic susceptibility to lead toxicity in the various population studies conducted worldwide and also to correlate it with the current scenario in Saudi Arabia. Such studies are necessary for appropriate precautions in terms of diet and avoiding exposure to be used in order to prevent adverse health effects. A. P. Shaik, S. A. Sultana, and A. H. Alsaeed Copyright © 2014 A. P. Shaik et al. All rights reserved. Association of the Three Common SNPs of Cyclooxygenase-2 Gene (rs20417, rs689466, and rs5275) with the Susceptibility of Breast Cancer: An Updated Meta-Analysis Involving 34,590 Subjects Mon, 18 Aug 2014 06:29:16 +0000 http://www.hindawi.com/journals/dm/2014/484729/ Several single nucleotide polymorphisms have been identified in cyclooxygenase-2 (COX-2) genes (e.g., −765 G>C (rs20417), −1195G>A (rs689466), and 8473 C>T (rs5275)). The association of these SNPs with the risk of different cancer types is still controversial. This study aims to evaluate the correlation between these SNPs and breast cancer risk in different ethnic groups. We have searched PubMed, Web of Knowledge, and Embase for relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the associations. A total of 13 studies (15,330 cases and 19,260 controls) were eligible for meta-analysis. This meta-analysis showed that COX-2 rs20417 polymorphism was correlated with an increased risk of breast cancer in Caucasians, while rs689466 was associated with a decreased risk of breast cancer in Caucasians. The rs5275 polymorphism had no association with breast cancer risk. Zhi-Jun Dai, Yong-Ping Shao, Xiao-Bin Ma, Dan Xu, Wei Tang, Hua-Feng Kang, Shuai Lin, Meng Wang, Hong-Tao Ren, and Xi-Jing Wang Copyright © 2014 Zhi-Jun Dai et al. All rights reserved. The Serum Glycome to Discriminate between Early-Stage Epithelial Ovarian Cancer and Benign Ovarian Diseases Tue, 12 Aug 2014 09:37:11 +0000 http://www.hindawi.com/journals/dm/2014/238197/ Epithelial ovarian cancer (EOC) is the sixth most common cause of cancer deaths in women because the diagnosis occurs mostly when the disease is in its late-stage. Current diagnostic methods of EOC show only a moderate sensitivity, especially at an early-stage of the disease; hence, novel biomarkers are needed to improve the diagnosis. We recently reported that serum glycome modifications observed in late-stage EOC patients by MALDI-TOF-MS could be combined as a glycan score named GLYCOV that was calculated from the relative areas of the 11 N-glycan structures that were significantly modulated. Here, we evaluated the ability of GLYCOV to recognize early-stage EOC in a cohort of 73 individuals comprised of 20 early-stage primary serous EOC, 20 benign ovarian diseases (BOD), and 33 age-matched healthy controls. GLYCOV was able to recognize stage I EOC whereas CA125 values were statistically significant only for stage II EOC patients. In addition, GLYCOV was more sensitive and specific compared to CA125 in distinguishing early-stage EOC from BOD patients, which is of high relevance to clinicians as it is difficult for them to diagnose malignancy prior to operation. Karina Biskup, Elena Iona Braicu, Jalid Sehouli, Rudolf Tauber, and Véronique Blanchard Copyright © 2014 Karina Biskup et al. All rights reserved. Association of Tagging SNPs in the MTHFR Gene with Risk of Type 2 Diabetes Mellitus and Serum Homocysteine Levels in a Chinese Population Wed, 06 Aug 2014 11:42:24 +0000 http://www.hindawi.com/journals/dm/2014/725731/ Diabetes is a global public health crisis, and the prevalence is increasing rapidly. Folate supplementation is proved to be effective in reducing the risk of diabetes or improving its symptoms. Methylenetetrahydrofolate reductase is an important enzyme involved in folate metabolism. The aim of this study is to examine whether polymorphisms in the MTHFR gene are associated with risk of type 2 diabetes mellitus (T2DM) and fasting total serum homocysteine (tHcy) levels. We genotyped nine tagging SNPs in the MTHFR gene in a case-control study, including 595 T2DM cases and 681 healthy controls in China. We found that C allele of rs9651118 had significant decreased risk of T2DM (adjusted odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.55–0.87, ) compared with T allele. Haplotype analysis also showed that MTHFR CTCCGA haplotype (rs12121543-rs13306553-rs9651118-rs1801133-rs2274976-rs1801131) had significant reduced risk of T2DM (adjusted OR = 0.71, 95% CI: 0.58–0.87, ) compared with CTTTGA haplotype. Besides, the MTHFR rs1801133 was significantly associated with serum levels of tHcy in healthy controls (). These associations were still significant after Bonferroni corrections (). These findings suggest that variants in the MTHFR gene may influence the risk of T2DM and tHcy levels. Han Wang, Cong Hu, Shu-Hui Xiao, and Bin Wan Copyright © 2014 Han Wang et al. All rights reserved. Antineutrophil Cytoplasmic Antibody Frequency in Chronic Hepatitis B Patients Tue, 05 Aug 2014 09:41:37 +0000 http://www.hindawi.com/journals/dm/2014/982150/ Background. Chronic hepatitis B (CHB) is a viral disease, common across the world, and associated with several extraintestinal manifestations including vasculitis. Antineutrophil cytoplasmic antibodies (ANCAs) are sensitive and specific markers for vasculitides. There is limited data available in the literature on whether ANCA formation is stimulated by CHB infection. In the present study we aimed to identify the frequency of ANCA in CHB patients. Methods. A total of 174 subjects were included in the study (87 CHB patients, 87 control subjects). Perinuclear-ANCA (P-ANCA), cytoplasmic-ANCA (C-ANCA), myeloperoxidase ANCA (MPO-ANCA), and proteinase 3-ANCA (PR3-ANCA) were studied. IFA was used for P-ANCA and C-ANCA assays, and ELISA was used for MPO-ANCA and PR3-ANCA assays. Results. ANCA positivity was high in both groups (31% in the CHB group and 26% among controls). There were no significant differences between the groups for P-ANCA and MPO-ANCA (P = 0.6 and P = 0.6, resp.). Frequency of borderline positive C-ANCA and all positive PR3-ANCA (positive + borderline positive) was significantly higher in the CHB group (P = 0.009 and P = 0.005, resp.). Conclusions. In the present study, the frequency of ANCA was high in both groups. The CHB group had a relatively higher frequency of ANCA positivity compared to controls. Borderline positive C-ANCA and positive PR3-ANCA were significantly higher in the CHB group. These results suggest that ANCA may have a high prevalence in Turkey. Patients with CHB should be evaluated particularly for C-ANCA and PR3-ANCA in the presence of vasculitic complaints and lesions. Turan Calhan, Abdurrahman Sahin, Resul Kahraman, Mustafa Erhan Altunoz, Fatma Ozbakır, Kamil Ozdil, and Hacı Mehmet Sokmen Copyright © 2014 Turan Calhan et al. All rights reserved. miR-146a Expression Level as a Novel Putative Prognostic Marker for Acute Promyelocytic Leukemia Tue, 05 Aug 2014 07:48:47 +0000 http://www.hindawi.com/journals/dm/2014/150604/ Background. Although the curative rate for acute promyelocytic leukemia (APL) has been improved over decades, long-term prognosis is still poor. The genetic pathways that regulated cell lineage fate during the development of APL remain unclear. Methods. We investigated the correlations of miR-146a expression with its target gene Smad4 and the biological behaviors of NB4 cells. We also analyzed their expression in clinical samples from APL patients. Results. miR-146a influenced apoptosis and proliferation in NB4 cells. miR-146a influenced endogenous Smad4 protein levels in APL cells. miR-146a expression levels were positively correlated with white cell counts and PML/RARα fusion protein expression. miR-146a expression levels were negatively correlated with Smad4 protein and the helper T cell (Th)/the suppressor T cell (Ts) ratio in these patients. Conclusions. These findings indicated that miR-146a played an important role in the development of APL in part through the repression on Smad4 protein expression. miR-146a functioned as an oncogene and may be a novel prognostic biomarker in APL. Lan Xu, Hua Zhong, Haixia Wan, Fang-yuan Chen, Jihua Zhong, Fei Xiao, Jia Liu, and Lijing Shen Copyright © 2014 Lan Xu et al. All rights reserved. Levels of Human Erythrocyte Membrane-Bound and Cytosolic Glycohydrolases Are Associated with Oxidative Stress in Erectile Dysfunction Patients Tue, 05 Aug 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/485917/ Oxidative stress (OS) and production of NO, by endothelium nitric oxide synthetase (eNOS), are involved in the pathophysiology of erectile dysfunction (ED). Moreover, OS induces modifications of the physicochemical properties of erythrocyte (RBC) plasma membranes and of the enzyme content of the same membranes. Due to their role in signalling early membrane alterations in OS-related pathologies, several plasma membrane and cytosolic glycohydrolases of human RBC have been proposed as new markers of cellular OS. In RBC, NOS can be activated and deactivated by phosphorylation/glycosylation. In this regulatory mechanism O-β-N-AcetylGlucosaminidase is a key enzyme. Cellular levels of O-GlcNAcylated proteins are related to OS; consequently dysfunctional eNOS O-GlcNAcylation seems to have a crucial role in ED. To elucidate the possible association between RBC glycohydrolases and OS, plasma hydroperoxides and antioxidant total defenses (Lag-time), cytosolic O-β-N-AcetylGlucosaminidase, cytosolic and membrane Hexosaminidase, membrane β-D-Glucuronidase, and α-D-Glucosidase have been studied in 39 ED patients and 30 controls. In ED subjects hydroperoxides and plasma membrane glycohydrolases activities are significantly increased whereas Lag-time values and cytosolic glycohydrolases activities are significantly decreased. These data confirm the strong OS status in ED patients, the role of the studied glycohydrolases as early OS biomarker and suggest their possible use as specific marker of ED patients, particularly in those undergoing nutritional/pharmacological antioxidant therapy. L. Massaccesi, G. V. Melzi d’Eril, G. M. Colpi, G. Tettamanti, G. Goi, and A. Barassi Copyright © 2014 L. Massaccesi et al. All rights reserved. The Role of Haptoglobin Genotypes in Chagas Disease Thu, 24 Jul 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/793646/ Although the number of people infected with T. cruzi is on the rise, host genetic and immune components that are crucial in the development of the Chagas disease have been discovered. We investigated the frequency of polymorphisms in the gene encoding haptoglobin of patients with chronic Chagas disease. The results suggest that while the HP1-1 genotype may confer protection against infection and the development of chronic Chagas disease due to the rapid metabolism of the Hp1-1-Hb complex and its anti-inflammatory activity, the presence of HP2-2 genotype may increase susceptibility towards a chronic condition of the disease due to a slow metabolism of the Hp2-2-Hb complex, lower antioxidant activity, and increased inflammatory reactivity, which lead to cell damage and a deterioration of the cardiac function. Finally, correlations between HP genotypes in different age groups and cardiac manifestations suggest that HP polymorphism could influence the prognosis of this infectious disease. This study shows some of the relevant aspects of the haptoglobin gene polymorphism and its implications in the T. cruzi infection. Ninomar Mundaray Fernández and Mercedes Fernández-Mestre Copyright © 2014 Ninomar Mundaray Fernández and Mercedes Fernández-Mestre. All rights reserved. Recipients with In Utero Induction of Tolerance Upregulated MHC Class I in the Engrafted Donor Skin Sun, 20 Jul 2014 12:11:47 +0000 http://www.hindawi.com/journals/dm/2014/531092/ The alterations in MHC class I expression play a crucial step in immune evasion of cancer or virus-infected cells. This study aimed to examine whether tolerized grafts modified MHC class I expression. FVB/N mice were rendered tolerant of C57BL/6 alloantigens by in utero transplantation of C57BL/6 marrows. Postnatally, engrafted donor skins and leukocytes were examined for their MHC expression by quantitative real-time PCR and flow cytometry. Engrafted donor skins upregulated their MHC class I related gene transcripts after short-term (1~2 weeks) or long-term (>1 month) engraftment. This biological phenomenon was simultaneously associated with upregulation of TAP1 gene transcripts, suggesting an important role of TAP1 in the regulation of MHC class I pathway. The surface MHC class I molecules of H-2 in engrafted donor leukocytes consistently showed overexpression. Conclusively, the induction of allograft tolerance involved biological modifications of donor transplants. The overexpression of MHC class I within engrafted transplants of tolerant mice might be used as the tolerance biomarkers for identifying a state of graft tolerance. Jeng-Chang Chen, Liang-Shiou Ou, Hsiu-Yueh Yu, Ming-Ling Kuo, Pei-Yeh Chang, and Hsueh-Ling Chang Copyright © 2014 Jeng-Chang Chen et al. All rights reserved. K-ras Mutational Status in Cytohistological Tissue as a Molecular Marker for the Diagnosis of Pancreatic Cancer: A Systematic Review and Meta-Analysis Wed, 16 Jul 2014 12:14:36 +0000 http://www.hindawi.com/journals/dm/2014/573783/ Background. More clinically meaningful diagnostic tests are needed in pancreatic cancer (PC). K-ras mutations are the most frequently acquired genetic alteration. Methods. Original research articles involving the diagnostic accuracy of K-ras mutation detection in PC were selected. Data were presented as forest plots and summary receiver operating characteristic (SROC) curve analysis was used to summarize the overall test performance. Results. We assessed 19 studies from 16 published articles. The reports were divided into three groups according to the process used to obtain the test material. The summary estimates for detecting K-ras status using an invasive method (fine needle aspiration (FNA), endoscopic retrograde cholangiopancreatography (ERCP), or surgery) were better than cytology: the pooled sensitivity was 77% (95% confidence interval (CI): 74–80%) versus 54% (95% CI: 47–61%); specificity was 88% (95% CI: 85–91%) versus 91% (95% CI: 83–96%); and diagnostic odds ratio (DOR) was 20.26 (11.40–36.03) versus 7.52 (95% CI: 2.80–20.18), respectively. When two procedures were combined, the diagnostic accuracy was markedly improved. Conclusions. The analysis of K-ras mutations in pancreatic tissue has a promising diagnostic significance in PC. Further valuable studies are needed. Jing Yang, Jingjing Li, Rong Zhu, Huawei Zhang, Yuanyuan Zheng, Weiqi Dai, Fan Wang, Miao Shen, Kan Chen, Ping Cheng, Yan Zhang, Chengfen Wang, Junshan Wang, Yujing Xia, Jie Lu, Yingqun Zhou, and Chuanyong Guo Copyright © 2014 Jing Yang et al. All rights reserved. Serum Interleukin 17 Levels in Patients with Crohn’s Disease: Real Life Data Wed, 16 Jul 2014 10:23:17 +0000 http://www.hindawi.com/journals/dm/2014/690853/ The aim of this study was to investigate serum IL17 levels in patients with Crohn’s disease (CD) and to investigate the relationship between serum IL17 levels with disease activity. Methods. Fifty patients with CD and sex- and age-matched 40 healthy controls were included in the study. The serum IL17 levels, complete blood count, blood chemistry, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured, and Crohn’s disease activity was calculated using Crohn’s disease activity index (CDAI). Results. The mean serum IL17 level of CD patients did not differ from those of healthy controls (). There was no difference between the mean serum IL levels of active CD patients and of quiescent CD patients (). However, the mean IL17 level of active patients was lower than of control subjects (). Serum IL17 was not correlated with inflammatory markers (ESR, CRP, white blood count, platelet count, and albumin) and CDAI. Conclusions. Peripheral blood serum IL17 levels of CD patients were not higher than of healthy controls, and also, serum IL17 level was not correlated with clinical disease activity. Peripheral IL17 measurement is not a useful tool for detecting and monitoring Crohn’s disease which is understood to have complex etiopathogenesis. Abdurrahman Sahin, Turan Calhan, Mustafa Cengiz, Resul Kahraman, Kubra Aydin, Kamil Ozdil, May Korachi, and H. Mehmet Sokmen Copyright © 2014 Abdurrahman Sahin et al. All rights reserved. Comparison of Different Blood Collection, Sample Matrix, and Immunoassay Methods in a Prenatal Screening Setting Tue, 15 Jul 2014 13:07:04 +0000 http://www.hindawi.com/journals/dm/2014/509821/ We compared how measurements of pregnancy-associated plasma protein A (PAPP-A) and the free beta subunit of human chorionic gonadotropin (fβ-hCG) in maternal blood are influenced by different methods for blood collection, sample matrix, and immunoassay platform. Serum and dried blood spots (DBS) were obtained by venipuncture and by finger prick of 19 pregnant women. PAPP-A and fβ-hCG from serum and from DBS were measured by conventional indirect immunoassay on an AutoDELFIA platform and by antibody microarray. We compared methods based on the recoveries for both markers as well as marker levels correlations across samples. All method comparisons showed high correlations for both marker concentrations. Recovery levels of PAPP-A from DBS were 30% lower, while those of fβ-hCG from DBS were 50% higher compared to conventional venipuncture serum. The recoveries were not affected by blood collection or immunoassay method. The high correlation coefficients for both markers indicate that DBS from finger prick can be used reliably in a prenatal screening setting, as a less costly and minimally invasive alternative for venipuncture serum, with great logistical advantages. Additionally, the use of antibody arrays will allow for extending the number of first trimester screening markers on maternal and fetal health. Jeroen L. A. Pennings, Jacqueline E. Siljee, Sandra Imholz, Sylwia Kuc, Annemieke de Vries, Peter C. J. I. Schielen, and Wendy Rodenburg Copyright © 2014 Jeroen L. A. Pennings et al. All rights reserved. Prognostic Value of VEGF in Patients Submitted to Percutaneous Coronary Intervention Mon, 07 Jul 2014 09:00:19 +0000 http://www.hindawi.com/journals/dm/2014/135357/ We examined the longitudinal changes of VEGF levels after percutaneous coronary intervention for predicting major adverse cardiac events (MACE) in coronary artery disease (CAD) patients. VEGF was measured in 94 CAD patients’ serum before revascularization, 1-month and 1-year after. Independently of clinical presentation, patients had lower VEGF concentration than a cohort of healthy subjects (median, IQ: 15.9, 9.0–264 pg/mL versus 419, 212–758 pg/mL; ) at baseline. VEGF increased to 1-month (median, IQ: 276, 167–498 pg/mL; ) and remained steady to 1-year (median, IQ: 320, 173–497 pg/mL; ) approaching control levels. Drug eluting stent apposition and previous medication intake produced a less steep VEGF evolution after intervention (). Baseline VEGF concentration <40.8 pg/mL conveyed increased risk for MACE in a 5-year follow-up. Results reflect a positive role of VEGF in recovery and support its importance in CAD prognosis. Catarina Ramos, Patrícia Napoleão, Mafalda Selas, Cláudia Freixo, Ana Maria Viegas Crespo, Miguel Mota Carmo, Rui Cruz Ferreira, and Teresa Pinheiro Copyright © 2014 Catarina Ramos et al. All rights reserved. Haplotype Map of Sickle Cell Anemia in Tunisia Wed, 02 Jul 2014 11:48:48 +0000 http://www.hindawi.com/journals/dm/2014/938301/ β-Globin haplotypes are important to establish the ethnic origin and predict the clinical development of sickle cell disease patients (SCD). To determine the chromosomal background of Tunisian sickle cell patients, in this first study in Tunisia, we have explored four polymorphic regions of β-globin cluster on chromosome 11. It is the 5′ region of β-LCR-HS2 site, the intervening sequence II (IVSII) region of two fetal ( and ) genes and the 5′ region of β-globin gene. The results reveal a high molecular diversity of a microsatellite configuration describing the sequences haplotypes. The linkage disequilibrium analysis showed various haplotype combinations giving 22 “extended haplotypes”. These results confirm the utility of the β-globin haplotypes for population studies and contribute to knowledge of the Tunisian gene pool, as well as establishing the role of genetic markers in physiopathology of SCD. Imen Moumni, Maha Ben Mustapha, Sarra Sassi, Amine Zorai, Ikbel Ben Mansour, Kais Douzi, Dorra Chouachi, Fethi Mellouli, Mohamed Bejaoui, and Salem Abbes Copyright © 2014 Imen Moumni et al. All rights reserved. The Clinicopathological Significance of miR-133a in Colorectal Cancer Tue, 01 Jul 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/919283/ This study determined the expression of microRNA-133a (MiR-133a) in colorectal cancer (CRC) and adjacent normal mucosa samples and evaluated its clinicopathological role in CRC. The expression of miR-133a in 125 pairs of tissue samples was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and correlated with patient’s clinicopathological data by statistical analysis. Endogenous expression levels of several potential target genes were determined by qRT-PCR and correlated using Pearson’s method. MiR-133a was downregulated in 83.2% of tumors compared to normal mucosal tissue. Higher miR-133a expression in tumor tissues was associated with development of distant metastasis, advanced Dukes and TNM staging, and poor survival. The unfavorable prognosis of higher miR-133a expression was accompanied by dysregulation of potential miR-133a target genes, LIM and SH3 domain protein 1 (LASP1), Caveolin-1 (CAV1), and Fascin-1 (FSCN1). LASP1 was found to possess a negative correlation (), whereas CAV1 exhibited a significant positive correlation (), and a stronger correlation was found in patients who developed distant metastases (). In addition, a negative correlation of FSCN1 was only found in nonmetastatic patients. In conclusion, miR-133a was downregulated in CRC tissues, but its higher expression correlated with adverse clinical characteristics and poor prognosis. Timothy Ming-Hun Wan, Colin Siu-Chi Lam, Lui Ng, Ariel Ka-Man Chow, Sunny Kit-Man Wong, Hung-Sing Li, Johnny Hon-Wai Man, Oswens Siu-Hung Lo, Dominic Foo, Alvin Cheung, Thomas Yau, Jensen Tung-Chung Poon, Ronnie Tung-Ping Poon, Wai-Lun Law, and Roberta Wen-Chi Pang Copyright © 2014 Timothy Ming-Hun Wan et al. All rights reserved. A New Susceptibility Locus for Myocardial Infarction, Hypertension, Type 2 Diabetes Mellitus, and Dyslipidemia on Chromosome 12q24 Thu, 26 Jun 2014 12:10:03 +0000 http://www.hindawi.com/journals/dm/2014/291419/ We examined the role of hepatic nuclear factor-1 alpha (HNF1a) gene polymorphism on coronary artery disease (CAD) traits in 4631 Saudi angiographed individuals (2419 CAD versus 2212 controls) using TaqMan assay on ABI Prism 7900HT sequence detection system. Following adjustment for confounders, the rs2259820_CC (1.19 (1.01–1.42); ), rs2464196_TT (1.19 (1.00–1.40); ), and rs2259816_T (1.13 (1.01–1.26); ) were associated with MI. The rs2259820_T (1.14 (1.03–1.26); ) and rs2464196_C (1.12 (1.02–1.24); ) were associated with type 2 diabetes mellitus (T2DM), while the rs2393791_T (1.14 (1.01–1.28); ), rs7310409_G (1.16 (1.03–1.30); ), and rs2464196_AG+GG (1.25 (1.05–1.49); ) were implicated in hypertension. Hypertriglyceridemia was linked to the rs2393791_T (1.14 (1.02–1.27); ), rs7310409_G (1.12 (1.01–1.25); ), rs1169310_G (1.15 (1.04–1.28); ), and rs1169313_CT+TT (1.24 (1.06–1.45); ) and high low density lipoprotein-cholesterol levels were associated with rs2259820_T (1.23 (1.07–1.41); ), rs2464196_T (1.22 (1.06–1.39); ), and rs2259816_T (1.18 (1.02–1.36); ). A 7-mer haplotype CATATAC (; ), constructed from the studied SNPs, was associated with MI, and CATATA implicated in T2DM (; ). Hypertriglyceridemia was linked to TGCGGG (; ), and obesity to ACGGGT (; ). Our results suggest that the HNF1a is a common susceptibility gene for MI, T2DM, hypertension, and dyslipidemia. Salma M. Wakil, Nzioka P. Muiya, Asma I. Tahir, Mohammed Al-Najai, Batoul Baz, Editha Andres, Nejat Mazhar, Nada Al Tassan, Maie Alshahid, Brian F. Meyer, and Nduna Dzimiri Copyright © 2014 Salma M. Wakil et al. All rights reserved. Urinary N-Acetyl-beta-D-glucosaminidase as an Early Marker for Acute Kidney Injury in Full-Term Newborns with Neonatal Hyperbilirubinemia Tue, 24 Jun 2014 12:12:46 +0000 http://www.hindawi.com/journals/dm/2014/315843/ Purpose. To investigate renal function estimated by markers in full-term newborns with hyperbilirubinemia. Methods. A total of 332 full-term newborns with hyperbilirubinemia and 60 healthy full-term newborns were enrolled. Total serum bilirubin, serum creatinine (Cr), serum blood urea nitrogen (BUN), serum cystatin C (Cys-C), urinary beta-2-microglobulin (β2MG) index, and urinary N-acetyl-beta-D-glucosaminidase (NAG) index were measured before and after treatment. All newborns were divided into three groups according to total serum bilirubin levels: group 1 (221-256), group 2 (256-342), and group 3 (>342). Results. The control group and group 1 did not differ significantly in regard to serum Cr, serum BUN, serum Cys-C, urinary β2MG index, and urinary NAG index. Urinary NAG index in group 2 was significantly higher than that in control group (). Between control group and group 3, serum Cys-C, urinary β2MG index, and urinary NAG index differed significantly. The significant positive correlation between total serum bilirubin and urinary NAG index was found in newborns when total serum bilirubin level was more than 272 μmol/L. Conclusions. High unconjugated bilirubin could result in acute kidney injury in full-term newborns. Urinary NAG might be the suitable marker for predicting acute kidney injury in full-term newborns with hyperbilirubinemia. Bangning Cheng, Yulian Jin, Guanghui Liu, Zhiheng Chen, Hongmei Dai, and Min Liu Copyright © 2014 Bangning Cheng et al. All rights reserved.