Association Testing of Common Variants in the Insulin Receptor Substrate-1 Gene (IRS1) with Type 2 Diabetes

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2007 Apr 20

PMID 17443311

Citations 4

Authors

J C Florez

M Sjogren

C M Agapakis

N P Burtt

P Almgren

U Lindblad

G Berglund

T Tuomi

D Gaudet

M J Daly

K G Ardlie

J N Hirschhorn

D Altshuler

L Groop

Affiliations

Soon will be listed here.

Abstract

Aims/hypothesis: Activation of the insulin receptor substrate-1 (IRS1) is a key initial step in the insulin signalling pathway. Despite several reports of association of the G972R polymorphism in its gene IRS1 with type 2 diabetes, we and others have not observed this association in well-powered samples. However, other nearby variants might account for the putative association signal.

Subjects And Methods: We characterised the haplotype map of IRS1 and selected 20 markers designed to capture common variations in the region. We genotyped this comprehensive set of markers in several family-based and case-control samples of European descent totalling 12,129 subjects.

Results: In an initial sample of 2,235 North American and Polish case-control pairs, the minor allele of the rs934167 polymorphism showed nominal evidence of association with type 2 diabetes (odds ratio [OR] 1.25, 95% CI 1.03-1.51, p = 0.03). This association showed a trend in the same direction in 7,659 Scandinavian samples (OR 1.16, 95% CI 0.96-1.39, p = 0.059). The combined OR was 1.20 (p = 0.008), but statistical correction for the number of variants examined yielded a p value of 0.086. We detected no differences across rs934167 genotypes in insulin-related quantitative traits.

Conclusions/interpretation: Our data do not support an association of common variants in IRS1 with type 2 diabetes in populations of European descent.

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