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

AbstractHere, we examined the association of genetic variants ofFOXA2, 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 thatFOXA2 variants may affect risk of type 2 diabetes and metabolic traits in North India, howe...
Source: Journal of Human Genetics - Category: Genetics & Stem Cells Source Type: research