%0 Journal Article
%T Circadian Gene Variants and Susceptibility to Type 2 Diabetes: A Pilot Study
%A M. Ann Kelly
%A Simon D. Rees
%A M. Zafar I. Hydrie
%A A. Samad Shera
%A Srikanth Bellary
%A J. Paul O¡¯Hare
%A Sudhesh Kumar
%A Shahrad Taheri
%A Abdul Basit
%A Anthony H. Barnett
%A DIAGRAM consortium
%A SAT2D consortium
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0032670
%X Background Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs) in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants. Methodology/Principal Findings The pilot study was performed using two genetically homogeneous Punjabi cohorts, one resident in the United Kingdom and one indigenous to Pakistan. Subjects with (N = 1732) and without (N = 1780) type 2 diabetes were genotyped for thirteen circadian variants using a competitive allele-specific polymerase chain reaction method. Associations between the SNPs and type 2 diabetes were investigated using logistic regression. The results were also combined with in silico data from other South Asian datasets (SAT2D consortium) and white European cohorts (DIAGRAM+) using meta-analysis. The rs7602358G allele near PER2 was negatively associated with type 2 diabetes in our Punjabi cohorts (combined odds ratio [OR] = 0.75 [0.66¨C0.86], p = 3.18¡Á10£¿5), while the BMAL1 rs11022775T allele was associated with an increased risk of the disease (combined OR = 1.22 [1.07¨C1.39], p = 0.003). Neither of these associations was replicated in the SAT2D or DIAGRAM+ datasets, however. Meta-analysis of all the cohorts identified disease associations with two variants, rs2292912 in CRY2 and rs12315175 near CRY1, although statistical significance was nominal (combined OR = 1.05 [1.01¨C1.08], p = 0.008 and OR = 0.95 [0.91¨C0.99], p = 0.015 respectively). Conclusions/significance None of the selected circadian gene variants was associated with type 2 diabetes with study-wide significance after meta-analysis. The nominal association observed with the CRY2 SNP, however, complements previous findings and confirms a role for this locus in disease susceptibility.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0032670