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BMC Medical Genetics

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Open Access 01-12-2005 | Research article

Insulin Promoter Factor 1 variation is associated with type 2 diabetes in African Americans

Authors: Mohammad A Karim, Xiaoqin Wang, Terri C Hale, Steven C Elbein

Published in: BMC Medical Genetics | Issue 1/2005

Abstract

Background

Defective insulin secretion is a key defect in the pathogenesis of type 2 diabetes (T2DM). The β-cell specific transcription factor, insulin promoter factor 1 gene (IPF1), is essential to pancreatic development and the maintenance of β-cell mass. We hypothesized that regulatory or coding variants in IPF1 contribute to defective insulin secretion and thus T2DM.

Methods

We screened 71 Caucasian and 69 African American individuals for genetic variants in the promoter region, three highly conserved upstream regulatory sequences (PH1, PH2 and PH3), the human β-cell specific enhancer, and the two exons with adjacent introns. We tested for an association of each variant with T2DM Caucasians (192 cases and 192 controls) and African Americans (341 cases and 186 controls).

Results

We identified 8 variants in the two populations, including a 3 bp insertion in exon 2 (InsCCG243) in African Americans that resulted in an in-frame proline insertion in the transactivation domain. No variant was associated with T2DM in Caucasians, but polymorphisms at -3766 in the human β-cell enhancer, at -2877 bp in the PH1 domain, and at -108 bp in the promoter region were associated with T2DM in African American subjects (p < 0.01), both individually and as haplotypes (p = 0.01 correcting by permutation test). No SNP altered a binding site for the expected β-cell transcription factors. The rare alleles of InsCCG243 in exon 2 showed a trend to over-representation among African American diabetic subjects (p < 0.1), but this trend was not significant on permutation test.

Conculsion

The common alleles of regulatory variants in the 5' enhancer and promoter regions of the IPF1 gene increase susceptibility to type 2 diabetes among African American individuals, likely as a result of gene-gene or gene-environment interactions. In contrast, IPF1 is not a cause of type 2 diabetes in Caucasians. A previously described InsCCG243 variant may contribute to diabetes susceptibility in African American individuals, but is of low penetrance.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/6/37/prepub

Title: Insulin Promoter Factor 1 variation is associated with type 2 diabetes in African Americans
Authors: Mohammad A Karim
Xiaoqin Wang
Terri C Hale
Steven C Elbein
Publication date: 01-12-2005
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2005
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-6-37

ACC 2024 Congress

Springer Medicine

Insulin Promoter Factor 1 variation is associated with type 2 diabetes in African Americans

Abstract

Background

Methods

Results

Conculsion

ACC 2024 Congress

Springer Medicine

Abstract

Background

Methods

Results

Conculsion

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