The A98V Single Nucleotide Polymorphism (SNP) in Hepatic Nuclear Factor 1 α (HNF-1α) is Associated with Insulin Sensitivity and β-Cell Function

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OBJECTIVE: Mutations in the hepatic nuclear factor-1-alpha ( HNF-1alpha) gene is considered as a candidate for the aetiology of type 2 diabetes. The aims of the study was to determine whether two single nucleotide polymorphisms (SNPs) ile27-to-leu and ala98-to-val in the HNF-1alpha gene associate with diabetes, insulin sensitivity as well as beta-cell function. RESEARCH DESIGN AND METHODS: 1 479 subjects of a volunteer sample with increased risk of type 2 diabetes were investigated. They underwent a 75 g oral glucose tolerance test (OGTT) with measurements of plasma glucose, insulin and C-peptide at fasting and at 30, 60, 90 and 120 minutes after the glucose challenge. The HNF-1alpha SNPs, I27L and A98V were genotyped. RESULT: Patients harbouring the V98 allele exhibited higher serum insulin and C-peptide levels. The heterozygote variant was also associated with decrease in beta-cell function but better insulin sensitivity. No significant differences of any clinical parameters were found for I27L gene variants. CONCLUSION: Significant associations between the heterozygote A98V genotype and clinical parameters of insulin metabolism were reported but no relationship with type 2 diabetes was obtained. This may be explained by a balancing negative effect on insulin secretion and concomitant positive effect on insulin resistance in Val allele carriers.

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