1. Circadian gene variants and susceptibility to type 2 diabetes : a pilot study
- Author
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Muhammad Zafar Hydrie, Eleftheria Zeggini, Anna Gloyn, Michael Weedon, Chidambaram Manickam, Torben Jørgensen, Amanda Bennett, Yurii Aulchenko, Andrew Hattersley, Christian Dina, Shahrad Taheri, Claudia Langenberg, SRIKANTH BELLARY, Rafn Benediktsson, Nabi Shah, Prasad Katulanda, Philippe Froguel, Cornelia Van Duijn, David Couper, Jana Van Vliet-Ostaptchouk, Winston Hide, Thomas Meitinger, Sudhesh Kumar, Richard Bergman, Cecilia Lindgren, and Igor Rudan
- Subjects
Male ,Genotyping Techniques ,Clinical Research Design ,lcsh:Medicine ,Single-nucleotide polymorphism ,Pilot Projects ,Disease ,Type 2 diabetes ,Biology ,Polymorphism, Single Nucleotide ,Endocrinology ,Gene Frequency ,Polymorphism (computer science) ,Risk Factors ,Diabetes mellitus ,medicine ,Genetics ,Humans ,Genetic Predisposition to Disease ,Circadian rhythm ,lcsh:Science ,QH426 ,Genetic Association Studies ,Diabetic Endocrinology ,Multidisciplinary ,Circadian Rhythm Signaling Peptides and Proteins ,Cancer Risk Factors ,lcsh:R ,Computational Biology ,Cancers and Neoplasms ,Human Genetics ,medicine.disease ,Genitourinary Tract Tumors ,Diabetes Mellitus, Type 2 ,Oncology ,Medicine ,lcsh:Q ,Female ,Metabolic syndrome ,TCF7L2 ,Population Genetics ,Research Article ,RC - Abstract
Background\ud 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.\ud \ud Methodology/Principal Findings\ud 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 [0.66–0.86], p = 3.18×10−5), while the BMAL1 rs11022775T allele was associated with an increased risk of the disease (combined OR = 1.22 [1.07–1.39], 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 [1.01–1.08], p = 0.008 and OR = 0.95 [0.91–0.99], p = 0.015 respectively).\ud \ud Conclusions/significance\ud 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.
- Published
- 2012