Genetic variants of FOXA2: risk of type 2 diabetes and effect on metabolic traits in North Indians.
Here, we examined the association of genetic variants of FOXA2, an upstream activator of the beta-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 x 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 x 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 x 10(-6)] and obese individuals [0.47 (95% CI 0.34-0.64), p = 4.3 x 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.
Tabassum
Rubina
R
Functional Genomics Unit, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi, 110 007, India.
Chavali
Sreenivas
S
Functional Genomics Unit, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi, 110 007, India.
Dwivedi
Om Prakash
OP
Functional Genomics Unit, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi, 110 007, India.
Tandon
Nikhil
N
Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, 110 029, India.
Bharadwaj
Dwaipayan
D
Functional Genomics Unit, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi, 110 007, India. db@igib.res.in.
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D001786:Blood Glucose; D002096:C-Peptide; C496502:FOXA2 protein, human; D007328:Insulin; D051542:Hepatocyte Nuclear Factor 3-beta
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