Gly972Arg variant in the insulin receptor substrate-1 gene and association with Type 2 diabetes: a meta-analysis of 27 studies

A. Jellema*, M.P.A. Zeegers, E. Feskens, P.C. Dagnelie, R.P. Mensink

*Corresponding author for this work

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Abstract

Gly972Arg variant in the insulin receptor substrate-1 gene and association with Type 2 diabetes: a meta-analysis of 27 studies.

Jellema A, Zeegers MP, Feskens EJ, Dagnelie PC, Mensink RP.

Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. a.jellema@hb.unimaas.nl

AIMS/HYPOTHESIS: Several case-control studies have examined the association between the Gly972Arg variant in the IRS-1 gene and Type 2 diabetes, but most had limited power and results could therefore be conflicting. METHODS: We systematically reviewed the literature by means of a meta-analysis and investigated sources of heterogeneity in results of different studies. RESULTS: The summary risk ratio, based on 3408 cases and 5419 control cases from 27 studies, was 1.25 (95% CI 1.05-1.48). The results, however, differed according to the type of study, method of verifying non-diabetic status of the control subjects, and age of the case subjects. Population-based studies reported lower odds ratios than hospital-based studies (OR 0.98, 95% CI 0.74-1.30 vs OR 1.43, 95% CI 1.17-1.74). Also, the diagnostic test to exclude diabetes amongst control subjects interacted with the association between the IRS-1 Gly972Arg variant and Type 2 diabetes (p=0.03). Finally, the odds ratio reduced with increasing age ( p=0.03). CONCLUSION/INTERPRETATION: Overall, carriers of the 972Arg variant of the IRS-1 gene are at a 25% increased risk of having Type 2 diabetes compared with non-carriers. The odds ratios are generally higher in hospital-based studies, including relatively young, symptomatic, cases
Original languageEnglish
Pages (from-to)990-995
Number of pages5
JournalDiabetologia
Volume46
Issue number7
DOIs
Publication statusPublished - 1 Jan 2003

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