Common genetic variation near melatonin receptor MTNR1B contributes to raised plasma glucose and increased risk of type-2 diabetes amongst Indian Asians and European whites.
- John C Chambers1,
- Weihua Zhang1,
- Delilah Zabaneh1,
- Joban Sehmi2,
- Piyush Jain2,
- Mark I McCarthy3,
- Philippe Froguel4,5,
- Aimo Ruokonen6,
- David Balding1,
- Marjo-Riitta Jarvelin1,7,
- James Scott2,
- Paul Elliott1 and
- Jaspal S Kooner (j.kooner{at}imperial.ac.uk)2
- 1 Department of Epidemiology and Public Health, Imperial College London, UK
- 2 National Heart and Lung Institute, Imperial College London, UK
- 3 Oxford Centre for Diabetes, Endocrinology and Metabolism and Oxford NIHR Biomedical Research Centre, UK
- 4 Section of Genomic Medicine, Imperial College London, UK and CNRS, 8090-Institute of Biology, Pasteur Institute, Lille, France
- 5 UMR 8090-Institute of Biology, Pasteur Institute, Lille, France
- 6 Department of Clinical Sciences/ Clinical Chemistry, University Hospital Oulu, Finland
- 7 Institute of Health Sciences and Biocenter Oulu, University of Oulu, Finland and Department of Child and Adolescent Health, National Institute of Health and Welfare, Finland
Abstract
Background: Fasting plasma glucose and risk of type-2 diabetes (T2D) are higher amongst Indian Asians than amongst European and North American whites. Few studies have investigated genetic factors influencing glucose metabolism amongst Indian Asians.
Methods: We carried out genome-wide association for fasting glucose in 5,089 non-diabetic Indian Asians genotyped with the Illumina Hap610 BeadChip, and 2,385 Indian Asians (698 with T2D) genotyped with the Illumina 300 BeadChip. Results were compared with findings in 4,462 European whites.
Findings: We identified three SNPs associated with glucose amongst 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 LD with rs1387153 (r2=0.60) and rs10830963 (r2=0.45), both previously associated with glucose in Europeans. Risk allele frequency and effect sizes for rs2166706 were similar amongst Indian Asians and Europeans: frequency 46.2% vs 45.0% respectively (P=0.44); effect 0.05 (95%CI 0.01-0.08) vs 0.05 (95%CI 0.03-0.07) mmol/L higher glucose per allele copy respectively (P=0.84). SNP rs2166706 was associated with T2D in Indian Asians (OR 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 amongst Indian Asians. Risk allele frequencies of rs1260326 (GCKR) and rs560887 (G6PC2) were higher amongst Indian Asians compared with Europeans.
Interpretation: Common genetic variation near MTNR1B influences blood glucose and risk of T2D in Indian Asians. Genetic variation at the MTNR1B, GCK, GCKR and G6PC2 loci may contribute to abnormal glucose metabolism and related metabolic disturbances amongst Indian Asians.
Footnotes
-
- Received December 29, 2008.
- Accepted July 13, 2009.
- Copyright © American Diabetes Association
