BACKGROUND:The VDR protein is at the centre of the vitamin D endocrine system, a complex physiological system with substantial feedback regulatory mechanisms involved in maintaining serum calcium and 1, 25 dihydroxy vitamin D3. Variations in VDR gene are shown to have implications in several diseases and have also been implicated as an important genetic factor affecting bone mass.AIM:To determine the frequency of Fok I and Taq I variants in healthy Indian individuals and its association with 25-OH-Vitamin D levels.SETTINGS AND DESIGN:Blood samples were collected from 143 unrelated normal individuals (Male-84 and Female-59) and their genotypes determined.MATERIALS AND METHODS:After amplification by polymerase chain reaction, each polymorphism was genotyped by restriction fragment length polymorphism. For 100 normal healthy individuals 25-hydroxyvitamin D estimation was done using DiaSorin kit method.STATISTICAL ANALYSIS:Graph pad software was used to calculate the P values from the Chi-square.RESULTS:Out of 143 samples analyzed for FokI and TaqI polymorphisms the following genotypic frequency was obtained FF 59%, Ff 36%, ff 5% and TT 49%, Tt 43%, tt 8% respectively.CONCLUSIONS:Results indicate that the distribution of the polymorphic loci Fok I and Taq I vary considerably not only in different populations, but also within India. Furthermore, when the genotypes were analyzed with respect to 25-OH-Vitamin D levels, a significant association was seen for the Taq 1 SNP but not with the Fok I.

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Highlights Hair cortisol concentration was associated with childhood adversity in one year olds in rural India. Saliva cortisol slope and area under the curve did not show this association. This is the largest study of hair cortisol in young children. This is the first study to report hair cortisol from a low/middle income country.

BackgroundProstate cancer (PCa) shows considerable clinical heterogeneity that has been primarily attributed to variable molecular alterations. TMPRSS2–ERG fusion is one such molecular subtype that has been associated with predominantly poor prognosis. More recently, a single nucleotide polymorphism (SNP) in the TMPRSS2 gene rs12329760 C>T (Met160Val) has been shown to positively correlate with the fusion status and also to be associated with increased risk for PCa. The aim of the present study is to determine the frequency of TMPRSS2–ERG fusion and association of rs12329760 in Indian PCa patients with fusion status.MethodsTMPRSS2–ERG fusion by fluorescence in situ hybridization was determined in 102 of 150 PCa biopsy-proven cases. Genotyping for rs12329760 was performed on the entire cohort of 150 cases by Sanger sequencing.ResultsTMPRSS2–ERG fusion was seen in 27 of 102 (26%) cases. Fusion-positive patterns in this study showed fusion by translocation in nine of 27 cases (33.5%), by deletion in six of 27 (22%) cases, and by insertion in 12 of 27 cases (44.5%). No association of the fusion status with Gleason Score, pattern, or perineural invasion was seen. The TMPRSS2 SNP rs12329760 ‘T’ allele was prevalent with a frequency of 0.27 in the PCa patients. The SNP was significantly associated with fusion [odds ratio (OR) = 2.176, 95% confidence interval (CI) = 1.012–4.684, P = 0.04], more specifically fusion by deletion (P = 0.04).ConclusionThe results provided here determine the frequency of TMPRSS2–ERG fusions (26%) in a fairly large cohort of Indian PCa cases and also the association of rs12329760 SNP with TMPRSS2–ERG fusion. No association with other clinico-pathological features was observed. Future studies with clinical outcomes are warranted in this population.

Coronary artery disease (CAD) arises due to a complex interplay between the environment and genetic factors. Alterations in many of the biomarkers such as lipids and lipoprotein levels are characteristic of CAD. The phenotypes themselves have genetic determinants, and many single-nucleotide polymorphisms (SNPs) have been identified which influence them. The current study aims to evaluate the effect of six common polymorphisms at four loci, lipoprotein lipase (D9N, N291S, S447X), apolipoprotein E (APOE), cholesteryl ester transfer protein (C277T), and endothelial nitric oxide synthase (E298D), on lipid and lipoprotein levels and its association with CAD. Genotyping for the SNPs was done in 240 Indians of which 90 had proven CAD. The other 150 were clinically free from CAD and acted as controls. Relation of genetic variants, clinical history, and biochemical parameters with CAD were analyzed by multiple regression analysis. The frequency of the B2 allele in the CETP gene was significantly lower in cases than in controls (0.40 vs 0.49, P = 0.042). Significant association of CETP Taq1B SNP was seen with total cholesterol and low density lipoprotein cholesterol. Multivariate analysis accounting for clinical and metabolic predictors of CAD showed smoking to be a significant risk factor (odds ratio (OR) 4.347, 95% confidence interval (CI) 1.888-10.012, P = 0.001) and the CETP B2 variant imparting atheroprotection (OR 0.312, 95% CI 0.116-0.841, P = 0.021) possibly through a favorable lipid profile. None of the other SNPs were associated with the risk of CAD.

INTRODUCTION:A central component of the atherosclerotic process is inflammation. Single nucleotide polymorphisms (SNPs) present in the promoter region of various cytokines can lead to altered levels of the transcript and a state of low-grade inflammation exacerbating the risk of coronary artery disease (CAD). The present work tries to understand the role of permissive promoter variants in the interleukin-6 gene (IL-6-174G/C) and the tumor necrosis factor alpha (TNFα-308G/A) in the causation of CAD and also dyslipidemia.MATERIALS AND METHODS:Genotyping was conducted on 100 cases of CAD and 150 controls by the allele termination assay SNaPshot. Biochemical parameters were determined by routine enzymatic endpoint methods. The results were analyzed by appropriate statistical methods.RESULTS:No differences in the minor allele frequency IL-6-174G/C SNP were seen between cases and controls (0.13 vs. 0.12). The differences in the allele frequency of TNFα-308A between cases (6%) and controls (2%) have led to an odds ratio, 3.370; 95% confidence interval, 1.039-11.543; P=0.033 in the univariate analysis. In the final logistic regression analysis, however none of the variants were associated with an increased risk of CAD.CONCLUSIONS:In summary, no association of the permissive promoter variants in the IL-6 gene and the TNFα gene were seen with an increased CAD risk. These and other studies highlight the importance of doing population specific studies.

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In summary, carriers of the KIF6 719Arg allele were not at increased risk of CAD/non-fatal MI in a case-control study of Indians (Indo-Europeans) living in Western India.