Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations

• Published in: Diabetologia 2011-06, Vol.54 (6), p.1368-1374
• Main Authors: Rees, S. D., Hydrie, M. Z. I., Shera, A. S., Kumar, S., O’Hare, J. P., Barnett, A. H., Basit, A., Kelly, M. A.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Asian Continental Ancestry Group - ethnology; Asian Continental Ancestry Group - genetics; Asian people; Biological and medical sciences; Case-Control Studies; Diabetes; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - ethnology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; DNA Replication - genetics; Endocrine pancreas. Apud cells (diseases); Endocrinology; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Genome-Wide Association Study; Genomes; Genotype; Glucose; Health risk assessment; Human Physiology; Humans; Insulin Receptor Substrate Proteins - genetics; Internal Medicine; KCNQ1 Potassium Channel - genetics; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Minority & ethnic groups; Neoplasm Proteins - genetics; Pakistan; Polymorphism; Polymorphism, Single Nucleotide - genetics; Reproducibility of Results; Risk Factors
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-011-2063-2

Aims/hypothesis Recent genome-wide association (GWA) studies and subsequent replication studies have greatly increased the number of validated type 2 diabetes susceptibility variants, but most of these have been conducted in European populations. Despite the high prevalence of the disease in South Asians, studies investigating GWA-validated type 2 diabetes risk variants in this ethnic group are limited. We investigated 30 single nucleotide polymorphisms (SNPs), predominantly derived from recent GWA studies, to determine if and to what extent these variants affect type 2 diabetes risk in two Punjabi populations, originating predominantly from the District of Mirpur, Pakistan. Methods Thirty SNPs were genotyped in 1,678 participants with type 2 diabetes and 1,584 normoglycaemic control participants from two populations; one resident in the UK and one indigenous to the District of Mirpur. Results SNPs in or near PPARG , TCF7L2 , FTO , CDKN2A/2B , HHEX/IDE , IGF2BP2 , SLC30A8 , KCNQ1 , JAZF1 , IRS1 , KLF14 , CHCHD9 and DUSP9 displayed significant ( p