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Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South Asians : ADCY5 and GLIS3 variants may predispose to type 2 diabetes

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Rees, Simon D., Hydrie, M. Zafar I., O'Hare, J. Paul, Kumar, Sudhesh, Shera, A. Samad, Basit, Abdul, Barnett, A. H. (Anthony H.), 1951- and Kelly, M. Ann. (2011) Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South Asians : ADCY5 and GLIS3 variants may predispose to type 2 diabetes. PLoS ONE, Vol.6 (No.9). ISSN 1932-6203

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Abstract

Background: The Meta-Analysis of Glucose and Insulin related traits Consortium (MAGIC) recently identified 16 loci robustly
associated with fasting glucose, some of which were also associated with type 2 diabetes. The purpose of our study was to
explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the
District of Mirpur, Pakistan.
Methodology/Principal Findings: Sixteen single nucleotide polymorphisms (SNPs) were genotyped in 1678 subjects with
type 2 diabetes and 1584 normoglycaemic controls from two Punjabi populations; one resident in the UK and one
indigenous to the District of Mirpur. In the normoglycaemic controls investigated for fasting glucose associations, 12 of 16
SNPs displayed b values with the same direction of effect as that seen in European studies, although only the SLC30A8
rs11558471 SNP was nominally associated with fasting glucose (b = 0.063 [95% CI: 0.013, 0.113] p = 0.015). Of interest, the
MTNR1B rs10830963 SNP displayed a negative b value for fasting glucose in our study; this effect size was significantly lower
than that seen in Europeans (p = 1.2961024). In addition to previously reported type 2 diabetes risk variants in TCF7L2 and
SLC30A8, SNPs in ADCY5 (rs11708067) and GLIS3 (rs7034200) displayed evidence for association with type 2 diabetes, with
odds ratios of 1.23 (95% CI: 1.09, 1.39; p = 9.161024) and 1.16 (95% CI: 1.05, 1.29; p = 3.4961023) respectively.
Conclusions/Significance: Although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose in our
study, the finding that 12 out of 16 SNPs displayed a direction of effect consistent with European studies suggests that a
number of these variants may contribute to fasting glucose variation in individuals of South Asian ancestry. We also provide
evidence for the first time in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2 diabetes.

Item Type: Journal Article
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine
Divisions: Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Non-insulin-dependent diabetes -- Genetic aspects, Panjabis (South Asian people) -- Health and hygiene -- Pakistan -- Mirpur
Journal or Publication Title: PLoS ONE
Publisher: Public Library of Science
ISSN: 1932-6203
Official Date: 20 September 2011
Volume: Vol.6
Number: No.9
Identification Number: 10.1371/journal.pone.0024710
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: Diabetes UK, Eli Lilly International Foundation
Grant number: 07/ 0003512 (DUK)
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URI: http://wrap.warwick.ac.uk/id/eprint/38319

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