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.

TitleCommon genetic variation near melatonin receptor MTNR1B contributes to raised plasma glucose and increased risk of type 2 diabetes among Indian Asians and European Caucasians.
Publication TypeJournal Article
Year of Publication2009
AuthorsChambers JC, Zhang W, Zabaneh D, Sehmi J, Jain P, McCarthy MI, Froguel P, Ruokonen A, Balding D, Jarvelin M-R, Scott J, Elliott P, Kooner JS
JournalDiabetes
Volume58
Issue11
Pagination2703-8
Date Published11/2009
ISSN1939-327X
KeywordsAdult, Aged, Asian Continental Ancestry Group, Blood Glucose, Blood Pressure, Diabetes Mellitus, Type 2, Diet, Environment, Europe, European Continental Ancestry Group, Female, Genetic Variation, Genome-Wide Association Study, Humans, Hypertension, India, Life Style, Male, Middle Aged, Polymorphism, Single Nucleotide, Receptor, Melatonin, MT2, Risk Factors
Abstract

OBJECTIVE: Fasting plasma glucose and risk of type 2 diabetes are higher among Indian Asians than among European and North American Caucasians. Few studies have investigated genetic factors influencing glucose metabolism among Indian Asians.

RESEARCH DESIGN AND METHODS: We carried out genome-wide association studies for fasting glucose in 5,089 nondiabetic Indian Asians genotyped with the Illumina Hap610 BeadChip and 2,385 Indian Asians (698 with type 2 diabetes) genotyped with the Illumina 300 BeadChip. Results were compared with findings in 4,462 European Caucasians.

RESULTS: We identified three single nucleotide polymorphisms (SNPs) associated with glucose among Indian Asians at P < 5 x 10(-8), all near melatonin receptor MTNR1B. The most closely associated was rs2166706 (combined P = 2.1 x 10(-9)), which is in moderate linkage disequilibrium with rs1387153 (r(2) = 0.60) and rs10830963 (r(2) = 0.45), both previously associated with glucose in European Caucasians. Risk allele frequency and effect sizes for rs2166706 were similar among Indian Asians and European Caucasians: frequency 46.2 versus 45.0%, respectively (P = 0.44); effect 0.05 (95% CI 0.01-0.08) versus 0.05 (0.03-0.07 mmol/l), respectively, higher glucose per allele copy (P = 0.84). SNP rs2166706 was associated with type 2 diabetes in Indian Asians (odds ratio 1.21 [95% CI 1.06-1.38] per copy of risk allele; P = 0.006). SNPs at the GCK, GCKR, and G6PC2 loci were also associated with glucose among Indian Asians. Risk allele frequencies of rs1260326 (GCKR) and rs560887 (G6PC2) were higher among Indian Asians compared with European Caucasians.

CONCLUSIONS: Common genetic variation near MTNR1B influences blood glucose and risk of type 2 diabetes in Indian Asians. Genetic variation at the MTNR1B, GCK, GCKR, and G6PC2 loci may contribute to abnormal glucose metabolism and related metabolic disturbances among Indian Asians.

DOI10.2337/db08-1805
Alternate JournalDiabetes
PubMed ID19651812
PubMed Central IDPMC2768158
Grant List1RL1MH083268-01 / MH / NIMH NIH HHS / United States
5R01HL087679-02 / HL / NHLBI NIH HHS / United States
G0500539 / / Medical Research Council / United Kingdom
G0600331 / / Medical Research Council / United Kingdom
G0601966 / / Medical Research Council / United Kingdom
G0700931 / / Medical Research Council / United Kingdom
G0801056 / / Medical Research Council / United Kingdom
GR069224 / / Wellcome Trust / United Kingdom
SP/04/002 / / British Heart Foundation / United Kingdom