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

Title: 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
Authors: Chambers, 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
Item Type: Journal Article
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 × 10−8, all near melatonin receptor MTNR1B. The most closely associated was rs2166706 (combined P = 2.1 × 10−9), which is in moderate linkage disequilibrium with rs1387153 (r2 = 0.60) and rs10830963 (r2 = 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.
Issue Date: 1-Nov-2009
Date of Acceptance: 13-Jul-2009
URI: http://hdl.handle.net/10044/1/72527
DOI: https://doi.org/10.2337/db08-1805
ISSN: 0012-1797
Publisher: American Diabetes Association
Start Page: 2703
End Page: 2708
Journal / Book Title: Diabetes
Volume: 58
Issue: 11
Copyright Statement: © 2009 American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: G0601966
G0700931
G0801056B
G0600331
G0801056
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
GENOME-WIDE ASSOCIATION
INSULIN-RESISTANCE
FASTING GLUCOSE
CIRCADIAN CLOCK
PREVALENCE
OBESITY
POPULATION
POLYMORPHISM
TOLERANCE
VARIANTS
Adult
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
Humans
Hypertension
Diabetes Mellitus, Type 2
Blood Glucose
Receptor, Melatonin, MT2
Diet
Risk Factors
Life Style
Environment
Blood Pressure
Polymorphism, Single Nucleotide
Adult
Aged
Middle Aged
Asian Continental Ancestry Group
European Continental Ancestry Group
India
Europe
Female
Male
Genetic Variation
Genome-Wide Association Study
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
GENOME-WIDE ASSOCIATION
INSULIN-RESISTANCE
FASTING GLUCOSE
CIRCADIAN CLOCK
PREVALENCE
OBESITY
POPULATION
POLYMORPHISM
TOLERANCE
VARIANTS
11 Medical and Health Sciences
Endocrinology & Metabolism
Publication Status: Published
Online Publication Date: 2009-11
Appears in Collections:National Heart and Lung Institute
Epidemiology, Public Health and Primary Care



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