Diabetes mellitus (DM) is an alarming threat to health of mankind, yet its pathogenesis is unclear. The purpose of this study was to find potential biomarkers to serve as indicators for the pathogenesis of DM in a time course manner. Based on our previous findings that oxidative stress occurred at week 8, aorta lysate and sera of 102 streptozotocin (STZ)-induced diabetic and 85 control male Sprague-Dawley rats were obtained at the 4th, 8th and 12th week after STZ injection. The protein profiles were studied employing surface-enhanced laser desorption/ionization time-of-flight mass spectrometry technology in attomole sensitivity range. In the aorta, a multiple biomarker panel was discovered at the 4th week. At the 8th week, 4 biomarkers were found, while at the 12th week, 3 biomarkers were identified. In the sera, a triplet of 3 peaks and 2 biomarkers were all discovered to have 100&#x25; classification accuracy rate to differentiate the DM and control groups at all time intervals. Besides, 2 biomarkers were also found to have high classification value at week 12. Comparing the aorta and sera from DM and non-DM rats, a bundle of potential biomarkers with significant changes in peak intensities and high classification values were found. Two of the serum biomarkers matched with islet amyloid polypeptide and resistin in the SWISS-PROT knowledgebase. Validation has been conducted using immunoassay kits. These potential biomarkers may provide valuable insight on the pathogenesis of DM and macrovascular complications.

William C. S. Cho

Tai-Tung Yip

Wai-Shing Chung

Albert W. N. Leung

Christopher H. K. Cheng

Kevin K. M. Yue

Potential Biomarkers Found by Protein Profiling May Provide Insight for the Macrovascular Pathogenesis of Diabetes Mellitus

A case-control study was conducted for analyzing the genetic polymorphisms of phase II metabolic enzymes in 97 patients with lung cancer and 197 healthy subjects from Han ethnic group of Hunan Province located in Central South China. The results showed that the frequencies of glutathione S-transferase (GST) M1-null (GSTM1-) or GSTT1-null (GSTT1-) genotype alone, or combined form of both in lung cancer patients were significantly higher than those of the controls. Genotypes of combining GSTP1 mutant/GSTM1(-) or GSTP1 mutant/GSTT1(-) led to high risk of lung cancer. Individuals carrying any two or all three of GSTM1(-), GSTT1(-) and GSTP1 mutant genotypes have a distinctly increased risk of lung cancer when compared to those with GSTM1 present (GSTM1+: GSTM1+/+ or GSTM1+/&#x2212;), GSTT1 present (GSTT1+: GSTT1+/+ or GSTT1+/&#x2212;) and GSTP1 wild genotypes. Furthermore, individuals possessing combined genotypes of N-acetyltransferase 2 (NAT2) rapid acetylator, GSTP1 mutant and both GSTT1(-) and GSTM1(-) have a remarkably higher lung cancer risk than those carrying combined NAT2 slow acetylator genotype, GSTP1 wild genotype and both GSTT1(+) and GSTM1(+) genotypes. All these findings suggest that the genetic polymorphisms of phase II metabolic enzymes affect the susceptibility of lung cancer in the Han ethnic group of Central South China.

Han-chun Chen

Yan-fei Cao

Wei-xin Hu

Xin-fa Liu

Qing-xia Liu

Ji Zhang

Jia Liu

Genetic Polymorphisms of Phase II Metabolic Enzymes and Lung Cancer Susceptibility in a Population of Central South China

Objective: Soluble CD40 ligand (sCD40L) has been suggested as a key mediator between inflammation and atherosclerosis, and the CD40-CD40L interaction has a role in atherosclerotic lesion progression. We evaluated if platelet released serum sCD40L and sCD40 levels differ between patients with early onset occlusive carotid artery disease and age-matched controls.Methods: sCD40L and sCD40 levels were measured in serum samples of 60 patients with occlusive carotid artery disease and 30 age-matched controls using ELISA. Degree of stenosis of the internal carotid artery (ICA), and intima-media thickness (IMT) in the common carotid artery were measured by high resolution ultrasound. Values are given as mean &#xb1; SD.Results: Mean age was 50.9 &#xb1; 3.5 and 50.1 &#xb1; 3.5 years in the patient and control groups. IMT was significantly thicker in patients than in controls (0.89 &#xb1; 0.14 vs. 0.78 &#xb1;0.12 mm, p = 0.0003). Serum levels of sCD40L were significantly higher (6.9 &#xb1; 5 vs. 4.5 &#xb1; 3.0 ng/mL, p = 0.038) in patients, whereas sCD40 did not differ significantly between patients and controls (85 &#xb1; 56.9 vs. 79.3 &#xb1; 18.7 pg/mL, p = 0.34). IMT did not correlate with sCD40L or sCD40 levels (R = &#x2212;0.03, p = 0.77; and R = 0.109, p = 0.308, respectively).Conclusions: sCD40L but not sCD40 levels are significantly higher in patients with occlusive carotid artery disease. Platelet derived sCD40L may be a key mediator among inflammation, thrombosis and atherosclerosis.

J&#xf3;zsef Balla

M&#xe1;ria T&#xfc;nde Magyar

D&#xe1;niel Bereczki

Attila Valikovics

Em&#xf6;ke Nagy

Erika Barna

Andr&#xe1;s P&#xe1;l

Gy&#xf6;rgy Balla

L&#xe1;szl&#xf3; Csiba

Gy&#xf6;rgy Blask&#xf3;

Serum Levels of Platelet Released CD40 Ligand Are Increased in Early Onset Occlusive Carotid Artery Disease

Bronchial asthma and juvenile idiopathic arthritis (JIA) are complex genetic diseases. As both represent chronic inflammatory diseases it is likely that they are at least partially influenced by the same genetic variants. One goal in dissecting the genetics of complex diseases is to identify a genetic risk profile. Therefore it is necessary to genotype polymorphisms in many different pathways. Thus we investigated 48 polymorphisms in 24 genes for association with asthma and/or JIA.Genotpying was performed on 231 asthmatic children, 86 children with JIA and 270 controls. Association analysis was performed by the Armitage&#x2019;s trend test. Furthermore haplotypes were calculated by FAMHAP.We found association of polymorphisms within IL-4, CTLA4 and TNFalpha with asthma and/or JIA. Furthermore, the polymorphisms showed an inverse distribution between children with asthma and JIA. However, we were not able to confirm association of most of the previously described candidate genes.We conclude from our data that it might be very difficult to identify genetic risk profiles for the development of asthma and/or JIA that would be valid across different populations. However, this study adds further evidence that the common genetic background of asthma and JIA is mainly based on polymorphisms in important TH1 and TH2 cytokines.

K. Schubert

H. von Bonnsdorf

M. Burke

I. Ahlert

S. Braun

R. Berner

K. A. Deichmann

A. Heinzmann

A Comprehensive Candidate Gene Study on Bronchial Asthma and Juvenile Idiopathic Arthritis

Objective: To determine the &#x3b2;-amyloid precursor protein (&#x3b2;APP) isoforms ratio as a risk factor for Alzheimer&#x2019;s Disease and to assess its relationship with demographic and genetic variables of the disease.Methods: Blood samples from 26 patients fulfilling NINCDS-ADRDA diagnostic criteria for AD and 46 healthy control subjects were collected for Western blotting for &#x3b2;APP. A ratio of &#x3b2;APP isoforms, in optical densities, between the upper band (130 Kd) and the lower bands (106&#x2013;110 Kd) was obtained. Odds ratios were obtained to determine risk factor of this component.Results: &#x3b2;APP ratio on AD subjects was lower than that of control subjects: 0.3662 &#xb1; 0.1891 vs. 0.6769 &#xb1; 0.1021 (mean &#xb1; SD, p&#x3c;0.05). A low &#x3b2;APP ratio (&#x3c;0.6) showed an OR of 4.63 (95&#x25; CI 1.45 &#xb1; 15.33). When onset of disease was taken into account, a &#x3b2;APP ratio on EOAD subjects of 0.3965 &#xb1; 0.1916 was found vs. 0.3445 &#xb1; 0.1965 on LOAD subjects (p&#x3e;0.05).Conclusions: Altered &#x3b2;APP isoforms is a high risk factor for Alzheimer&#x2019;s disease, although it has no influence on the time of onset of the disease.

V. J. S&#xe1;nchez-Gonz&#xe1;lez

G. G. Ortiz

P. Gallegos-Arreola

M. A. Mac&#xed;as-Islas

E. D. Arias-Merino

V. Loera-Casta&#xf1;eda

E. Mart&#xed;nez-Cano

I. E. Vel&#xe1;zquez-Brizuela

S. A. Rosales-Corral

C. R. Curiel-Ortega

F. Pacheco-Mois&#xe9;s

J. J. Garc&#xed;a

Altered &#x3b2;-Amyloid Precursor Protein Isoforms in Mexican Alzheimer&#x2019;s Disease Patients

Aim: We investigated on parental history and IgE serum level in 2588 consecutive newborns to individuate babies &#x201c;at risk&#x201d; of atopy at birth and we analysed the polymorphisms of class III region to evaluate the association with immunogenetic markers of HLA: C4A, C4B, LTA, RAGE and TNFA genes; we performed TNF and IgE receptor (FCERB1) physiologically related gene polymorphisms.Result: 791 babies/2588 (30.6&#x25;) were considered &#x201c;at risk&#x201d; for atopy and followed-up: 400 had familial history of atopy (at least one parent or sibling), 256 had IgE &#x3e; 0.35 kUA/l at birth and during the follow-up and 135 were positive for both conditions.The allele C4B2 was significantly more frequent in the sample of babies at risk (22.1&#x25; vs 10&#x25;, p &#x3c; 0.001). Furthermore, the mean value of IgE at birth in babies carrying the allele C4B2 was 2.26 KUA/l versus 0.74 KUA/l in those not carrying this allele (p = 0.01). No signiﬁcant association emerged for RAGE at the centromeric end of class III region and for LTA, TNFA at the telomeric one. TNFRI, TNFRII and FCERB1 gene polymorphisms also seemed not implicated.Conclusion: Our study confirms that HLA class III region seems involved in familial predisposition to atopy, and C4B gene probably acts as a marker of a more restricted subregion.

A. De Silvestri

C. Belloni

M. De Amici

P. Mazzola

M. Zorzetto

M. Martinetti

L. Salvaneschi

M. Cuccia

Non Classical HLA Genes and Non-HLA Genes in a Population of Infants at Familial Risk of Atopy

Michael G. Harrington

Alfred N. Fonteh

Roger G. Biringer

Andreas F. R. H&#xfc;hmer

Disease Markers of the Nervous System

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Disease Markers publishes papers related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.

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Chief Editor Paola Gazzaniga is an Associate Professor in the Department of Molecular Medicine at Sapienza University of Rome, Italy. Her core research focuses on liquid biopsies in patients with solid tumors.

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Disease Markers publishes papers related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.

Disease Markers