A single-nucleotide polymorphism in a methylatable Foxa2 binding site of the G6PC2 promoter is associated with insulin secretion in vivo and increased promoter activity in vitro.

ABSTRACT:

Objective

The G6PC2 gene encoding islet-specific glucose-6-phosphatase related protein (IGRP) has a common promoter variant, rs573225 (-231G/A), located within a Foxa binding site. We tested the cis-regulatory effects of rs573225 on promoter activity and its association with insulin response to oral glucose.

Research design and methods

Functional effects of rs573225 were explored in transfected INS-1 and HIT-T beta-cell lines. A total of 734 young obese subjects of European ancestry were genotyped for rs573225. Insulin and glucose levels were measured in response to oral glucose, and the insulinogenic index (IGI) of insulin secretion was calculated.

Results

In vitro, the G allele showed a higher affinity for binding Foxa2 transcription factor and increased G6PC2 promo

SUBMITTER: Dos Santos C 

PROVIDER: S-EPMC2628624 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature