Journal Article

Genetic variants of FOXA2: risk of type 2 diabetes and effect on metabolic traits in North Indians

Chavali, Sreenivas, Bharadwaj, Dwaipayan, Tabassum, Rubina, Tandon, Nikhil, Dwivedi, Om Prakash

2008

نظرة عامة

Here, we examined the association of genetic variants of FOXA2 , an upstream activator of the β-cell transcription factor network, with type 2 diabetes and related phenotypes in North India. We genotyped three SNPs (rs1212275, rs1055080, rs6048205) and the (TCC) n repeat polymorphism in 1,656 participants comprising 1,031 patients with type 2 diabetes and 625 controls. SNPs rs1212275 and rs6048205 were uncommon (MAF < 5%) with similar distribution among patients and controls. We found a strong association of (TCC) n common allele A5 with type 2 diabetes [OR = 1.66 (95% CI 1.36–2.04, p  = 5.9 × 10 −7 ) for A5 homozygotes]. Obese individuals with A5A5 genotype had enhanced risk when segregated from normal-weight subjects [OR = 1.92 (95% CI 1.47–2.51), p  = 1.6 × 10 −6 ]. A5 was also nominally associated with higher fasting glucose ( p  = 0.02) and lower fasting insulin ( p  = 0.0028) and C-peptide ( p  = 0.036) levels among controls. At the rs1055080 locus, GG was found to provide reduced risk among normal-weight subjects [OR = 0.59 (95% CI 0.40–0.88), p  = 0.011]. Combination of protective GG and non-risk genotypes of (TCC) n showed reduced risk of type 2 diabetes both among normal-weight [OR = 0.43 (95% CI 0.29–0.65), p  = 1.2 × 10 −6 ] and obese individuals [0.47 (95% CI 0.34–0.64), p  = 4.3 × 10 −5 ]. For the first time we demonstrated that FOXA2 variants may affect risk of type 2 diabetes and metabolic traits in North India, however replication analyses in other cohorts are required to confirm the findings.

• الناشر: Springer Japan,Nature Publishing Group
• موضوع: Adult / Beta cells / Biomedicine / Blood Glucose - metabolism / C-Peptide - blood / Case-Control Studies / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - epidemiology / Diabetes Mellitus, Type 2 - genetics / Fasting / Female / Gene Expression / Gene Function / Gene polymorphism / Gene Therapy / Genetic diversity / Genetic Predisposition to Disease / Genotype / Hepatocyte Nuclear Factor 3-beta - genetics / Homozygotes / Human Genetics / Humans / India - epidemiology / Insulin / Insulin - blood / Laboratory testing / Male / Metabolism / Middle Aged / Molecular Medicine / Obesity - genetics / Original Article / Phenotypes / Polymerase Chain Reaction / Polymorphism, Genetic - genetics / Risk Factors / Single-nucleotide polymorphism