Circadian gene variants and susceptibility to type 2 diabetes: a pilot study.
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 sel...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3317653?pdf=render |
| _version_ | 1811206136754339840 |
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| author | M Ann Kelly Simon D Rees M Zafar I Hydrie A Samad Shera Srikanth Bellary J Paul O'Hare Sudhesh Kumar Shahrad Taheri Abdul Basit Anthony H Barnett DIAGRAM Consortium SAT2D Consortium |
| author_facet | M Ann Kelly Simon D Rees M Zafar I Hydrie A Samad Shera Srikanth Bellary J Paul O'Hare Sudhesh Kumar Shahrad Taheri Abdul Basit Anthony H Barnett DIAGRAM Consortium SAT2D Consortium |
| author_sort | M Ann Kelly |
| collection | DOAJ |
| description | 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.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).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. |
| first_indexed | 2024-04-12T03:42:47Z |
| format | Article |
| id | doaj.art-09e23ba8822b4ec5b81317635c37f156 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T03:42:47Z |
| publishDate | 2012-01-01 |
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| spelling | doaj.art-09e23ba8822b4ec5b81317635c37f1562022-12-22T03:49:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3267010.1371/journal.pone.0032670Circadian gene variants and susceptibility to type 2 diabetes: a pilot study.M Ann KellySimon D ReesM Zafar I HydrieA Samad SheraSrikanth BellaryJ Paul O'HareSudhesh KumarShahrad TaheriAbdul BasitAnthony H BarnettDIAGRAM ConsortiumSAT2D ConsortiumDisruption 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.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).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.http://europepmc.org/articles/PMC3317653?pdf=render |
| spellingShingle | M Ann Kelly Simon D Rees M Zafar I Hydrie A Samad Shera Srikanth Bellary J Paul O'Hare Sudhesh Kumar Shahrad Taheri Abdul Basit Anthony H Barnett DIAGRAM Consortium SAT2D Consortium Circadian gene variants and susceptibility to type 2 diabetes: a pilot study. PLoS ONE |
| title | Circadian gene variants and susceptibility to type 2 diabetes: a pilot study. |
| title_full | Circadian gene variants and susceptibility to type 2 diabetes: a pilot study. |
| title_fullStr | Circadian gene variants and susceptibility to type 2 diabetes: a pilot study. |
| title_full_unstemmed | Circadian gene variants and susceptibility to type 2 diabetes: a pilot study. |
| title_short | Circadian gene variants and susceptibility to type 2 diabetes: a pilot study. |
| title_sort | circadian gene variants and susceptibility to type 2 diabetes a pilot study |
| url | http://europepmc.org/articles/PMC3317653?pdf=render |
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