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Author  |
Kelly, M.A.; Rees, S.D.; Hydrie, M.Z.I.; Shera, A.S.; Bellary, S.; O'Hare, J.P.; Kumar, S.; Taheri, S.; Basit, A.; Barnett, A.H. |
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Title |
Circadian gene variants and susceptibility to type 2 diabetes: a pilot study |
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Journal Article |
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Year |
2012 |
Publication |
PloS one |
Abbreviated Journal |
PLoS One |
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Volume |
7 |
Issue |
4 |
Pages |
e32670 |
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Keywords |
Circadian Rhythm Signaling Peptides and Proteins/*genetics; Diabetes Mellitus, Type 2/*genetics; Female; Gene Frequency; Genetic Association Studies; *Genetic Predisposition to Disease; Genotyping Techniques; Humans; Male; Pilot Projects; *Polymorphism, Single Nucleotide; Risk Factors |
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Abstract |
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 [0.66-0.86], p = 3.18 x 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). 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. |
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Address |
College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. m.a.kelly@bham.ac.uk |
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Corporate Author |
SAT2D Consortium |
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Language |
English |
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ISSN |
1932-6203 |
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Notes |
PMID:22485135; PMC3317653 |
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Call Number |
HUNT @ maria.stuifbergen @ |
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1536 |
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