International Journal of Medical Genetics The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. The Association of 5-HTTLPR XLL Genotype with Higher Cortisol Levels in African Americans Thu, 08 Jan 2015 06:47:00 +0000 Genetic variants of the human serotonin transporter (SERT) may contribute to HPA axis dysregulation. SERT has two promoter region polymorphisms (5-HTTLPR: VNTR and SNP: rs25531), which may alter levels of SERT protein and its function. Combining these polymorphisms creates a functional polymorphism (FN) which may modulate mRNA expression. This study examines the relationship between these genetic variants and morning and evening salivary samples of both cortisol and dehydroepiandrosterone sulfate (DHEAS) concentrations in 269 African American (AA) adults. Resultant allele frequencies for the VNTR, SNP, and FN genotypes were 70% L (2% XLL), 84% A, and 54% LA (2% XLLA), respectively. The XLL genotype was associated with significantly higher concentrations of cortisol (~3X) and DHEAS (~2X) for both VNTR and FN polymorphisms. No significant differences were found for SNP genotypes. Conclusions were that persons with VNTR and FN XLL polymorphisms had significantly higher cortisol and DHEAS concentrations than other genotypes. AAs also appear to have a higher frequency of the rare XL allele than Caucasians. Whether the XLL genotype predisposes AAs to greater health challenges will require further research to determine the implications of these findings. Carmen L. Contreras-Sesvold, Preetha Abraham, Joseph M. Devaney, Brennan T. Harmon, and Patricia A. Deuster Copyright © 2015 Carmen L. Contreras-Sesvold et al. All rights reserved. Evidence for Central Asian Origin of the p.Val27Ile Variant in the GJB2 Gene Sun, 07 Dec 2014 14:01:14 +0000 The mutations in the GJB2 gene are the most common cause of nonsyndromic hearing impairment and they are associated with the population’s ethnic background. The p.Val27Ile is frequent in both Asia and America. In this retrospective study, we report the findings from the GJB2 screening and the audiological exams conducted on 125 Mexican mestizo patients with non-syndromic hearing impairment; they were treated at the Instituto Nacional de Rehabilitacion in Mexico City. The most frequent audiometric findings were bilateral, symmetrical, and profound hearing impairment. The allele frequencies in the GJB2 screening were p.Val27Ile 15%, other mutations 5%, and wild type 80%. We found no correlation between GJB2 genotype and auditory phenotype. The high allele frequency of p.Val27Ile was a very interesting finding. Our research suggests that p.Val27Ile arose in an ancient common ancestor who lived in Altai Republic and then the polymorphism was brought to America by its first inhabitants, the Amerindians. These results enhance our understanding of the peopling of the America, which remains unresolved. Guille García Sánchez, Alfonso Alfaro-Rodríguez, and Adrián Poblano Copyright © 2014 Guille García Sánchez et al. All rights reserved. Genetic Variants in the SORL1 Gene Are Associated with Age at Onset of Alzheimer Disease: A Survival Analysis Tue, 12 Aug 2014 11:00:00 +0000 Few studies focused on the association of SORL1 with the age at onset (AAO) of Alzheimer disease (AD). This study investigated the association of 43 SNPs in SORL1 with the AAO of AD by using the Kaplan-Meier survival analysis and the Cox proportional hazards model in SAS version 9.2 and linear regression model in PLINK software (791 AD patients and 782 controls). Both logrank test and Cox regression model showed that five SNPs (rs1784934, rs676759, rs560573, rs593769, and rs11218313) were associated with the AAO of AD in the male sample, while one SNP (rs17125558) was associated with the AAO of AD in the female sample (). SNP rs560573, previously associated with the risk of late-onset AD, showed the most association with the AAO in the male sample ( for logrank test and in the Cox model). The mean AAO was approximately 2.5 years earlier in individuals who were homozygous for the minor allele compared with those who had at least one major allele. Linear regression model showed that rs2282649 and rs726601 were associated with AAO in the whole sample ( and 0.0367, resp.). These findings provide evidence of several genetic variants in SORL1 influencing the AAO of AD. Ke-Sheng Wang, Xuefeng Liu, Liang Wang, David Briones, and Chun Xu Copyright © 2014 Ke-Sheng Wang et al. All rights reserved. Genetic Markers of Polycystic Ovary Syndrome: Emphasis on Insulin Resistance Sun, 03 Aug 2014 11:36:21 +0000 Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of childbearing age causing not only reproductive but also metabolic anomalies. PCOS women present with ovulatory dysfunction, abnormal hormones, hyperandrogenemia, obesity, and hyperinsulinemia. It is a heterogeneous disorder which results from interaction of multiple genes along with environmental factors. Insulin resistance is a central key element contributing to PCOS pathogenesis and is further aggravated by obesity. Insulin regulates metabolic homeostasis and contributes to ovarian steroidogenesis. Candidate gene analyses have dissected genes related to insulin secretion and action for their association with PCOS susceptibility. Although a large number of genomic variants have been shown to be associated with PCOS, no single candidate gene has emerged as a convincing biomarker thus far. This may be attributed to large amount of heterogeneity observed in this disorder. This review presents an overview of the polymorphisms in genes related to insulin signaling and their association with PCOS and its related traits. Nuzhat Shaikh, Roshan Dadachanji, and Srabani Mukherjee Copyright © 2014 Nuzhat Shaikh et al. All rights reserved. The Role of Transforming Growth Factor-Beta in Diabetic Nephropathy Tue, 28 Jan 2014 14:03:22 +0000 Several studies have demonstrated that chronic and low-grade inflammation is closely linked to type 2 diabetes mellitus. The associated mechanisms are related to synthesis and release of proinflammatory and anti-inflammatory cytokines, mainly by the adipose tissue. Moreover, there are evidences that cytokines and adhesion molecules are important for development of diabetic nephropathy. Among the cytokines associated with inflammatory responses in type 2 diabetes mellitus, the transforming growth factor-β (TGF-β) has been recognized as a central player in the diabetic nephropathy being involved in the development of glomerulosclerosis and interstitial fibrosis, as observed in the course of end-stage renal disease. Although TGF-β1 is classically an anti-inflammatory immune mediator it has been shown that in the presence of IL-6, which increases before the onset of T2D, TGF-β1 favors the differentiation of T helper 17 (Th17) cells that are activated in many pro-inflammatory conditions. Since TGF-β1 mRNA and consequently serum TGF-β1 levels are under genetic control, this review aims to discuss the relationship of TGF-β1 levels and polymorphisms in the development of nephropathy in type 2 diabetes mellitus. Karina Braga Gomes, Kathryna Fontana Rodrigues, and Ana Paula Fernandes Copyright © 2014 Karina Braga Gomes et al. All rights reserved.