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


CONCLUSIONS
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.
Jellema
A
A
Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. a.jellema@hb.unimaas.nl
Zeegers
M P A
MP
Feskens
E J M
EJ
Dagnelie
P C
PC
Mensink
R P
RP
D019943:Amino Acid Substitution / Q000235:genetics*; D001120:Arginine / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D006580:Genetic Carrier Screening; D014644:Genetic Variation / Q000235:genetics*; D005998:Glycine / Q000235:genetics; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D009765:Obesity; D016017:Odds Ratio; D010750:Phosphoproteins / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics
C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D001120:Arginine; D005998:Glycine