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

Preview

PDF WRAP_Kumar_journal.pone.0024710.pdf - Published Version - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader Download (463Kb)

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
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)
References:	1. Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, et al. (2010) New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 42: 105–116. ng.520 [pii];10.1038/ng.520 [doi]. 2. Bellary S, O’Hare JP, Raymond NT, Gumber A, Mughal S, et al. (2008) Enhanced diabetes care to patients of south Asian ethnic origin (the United Kingdom Asian Diabetes Study): a cluster randomised controlled trial. Lancet 371: 1769–1776. 3. Rees SD, Hydrie MZ, Shera AS, Kumar S, O’Hare JP, et al. (2011) Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations. Diabetologia;10.1007/s00125-011-2063-2 [doi]. 4. Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15: 539–553. 5. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21: 263–265. 6. Rees SD, Bellary S, Britten AC, O’Hare JP, Kumar S, et al. (2008) Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population. BMC Med Genet 9: 8. 7. Purcell S, Cherny SS, Sham PC (2003) Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19: 149–150. 8. Gauderman W, Morrison J QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies, http://hydra.usc.edu/ gxe. 9. Chambers JC, Zhang W, Zabaneh D, Sehmi J, Jain P, et al. (2009) Common genetic variation near melatonin receptor MTNR1B contributes to raised plasma glucose and increased risk of type 2 diabetes among Indian Asians and European Caucasians. Diabetes 58: 2703–2708. db08-1805 [pii];10.2337/db08- 1805 [doi]. 10. The International HapMap Consortium (2003) The International HapMap Project. Nature 426: 789–796. 11. Been LF, Hatfield JL, Shankar A, Aston CE, Ralhan S, et al. (2011) A low frequency variant within the GWAS locus of MTNR1B affects fasting glucose concentrations: Genetic risk is modulated by obesity. Nutr Metab Cardiovasc Dis;S0939–4753(11)00022-6 [pii];10.1016/j.numecd.2011.01.006 [doi]. 12. Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, et al. (2010) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 42: 579–589. 13. Freathy RM, Mook-Kanamori DO, Sovio U, Prokopenko I, Timpson NJ, et al. (2010) Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nat Genet 42: 430–435. ng.567 [pii];10.1038/ng.567 [doi]. 14. Kang HS, ZeRuth G, Lichti-Kaiser K, Vasanth S, Yin Z, et al. (2010) Glisimilar (Glis) Kruppel-like zinc finger proteins: insights into their physiological functions and critical roles in neonatal diabetes and cystic renal disease. Histol Histopathol 25: 1481–1496. 15. Kang HS, Kim YS, ZeRuth G, Beak JY, Gerrish K, et al. (2009) Transcription factor Glis3, a novel critical player in the regulation of pancreatic beta-cell development and insulin gene expression. Mol Cell Biol 29: 6366–6379. MCB.01259-09 [pii];10.1128/MCB.01259-09 [doi]. 16. Senee V, Chelala C, Duchatelet S, Feng D, Blanc H, et al. (2006) Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. Nat Genet 38: 682–687. ng1802 [pii];10.1038/ ng1802 [doi]. 17. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, et al. (2009) Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 41: 703–707. ng.381 [pii];10.1038/ng.381 [doi]. 18. Hu C, Zhang R, Wang C, Wang J, Ma X, et al. (2010) Variants from GIPR, TCF7L2, DGKB, MADD, CRY2, GLIS3, PROX1, SLC30A8 and IGF1 are associated with glucose metabolism in the Chinese. PLoS One 5: e15542. 10.1371/journal.pone.0015542 [doi].
URI:	http://wrap.warwick.ac.uk/id/eprint/38319

Request changes to a record

Actions (login required)

View Item