Back to Search
Start Over
Circadian gene variants and susceptibility to type 2 diabetes : a pilot study
- Source :
- PLoS ONE, PLoS ONE, Vol 7, Iss 4, p e32670 (2012)
- Publication Year :
- 2012
- Publisher :
- PLOS, 2012.
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, PLoS ONE, Vol 7, Iss 4, p e32670 (2012)
- Accession number :
- edsair.doi.dedup.....e8052f1bf9d6587c4137a819ec8bb8fb