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Title: Codon 972 polymorphism in the insulin receptor substrate-1 gene, obesity, and risk of noninsulin-dependent diabetes mellitus

Abstract

Because of the role of insulin receptor substrate-1 in insulin action, the insulin receptor substrate-1 gene is a candidate gene for noninsulin-dependent diabetes mellitus (NIDDM). Modest associations between NIDDM and a GGG-AGG single base substitution (corresponding to a glycine-arginine amino acid substitution) in codon 972 of the gene have been found, but none reached statistical significance. To examine further how large a proportion of NIDDM cases could be caused by the mutation, we performed a stratified analysis combining the results from the 6 earlier studies and those from our panel of 192 unrelated NIDDM subjects and 104 healthy controls. In addition, we looked for a possibility that the codon 972 mutation plays a role only in the presence of certain conditions. Genomic DNA samples obtained from NIDDM cases and healthy controls were genotyped using a PCR-restriction fragment length polymorphism protocol modified for genomic DNA. The GGG{r_arrow}AGG substitution was found in 5.7% of the diabetic subjects (11 of 192) and 6.9% of the controls (7 of 104). The difference between groups was not statistically significant, and it was not different from the results of other studies. The Mantel-Haenszel summary odds ratio across all studies was 1.49 (P < 0.05; 95% confidencemore » intervals, 1.01-2.2). This summary odds ratio is consistent with a small proportion of NIDDM cases ({approximately}3%) being caused by the mutation. Exploratory subgroup analyses on our panel suggested a clustering of NIDDM, the codon 972 mutation, and overweight, raising the hypothesis that the mutation may predispose to NIDDM only in the presence of excess body weight. 9 refs., 2 tabs.« less

Authors:
; ; ;  [1]
  1. Joslin Diabetes Center, Boston, MA (United States)
Publication Date:
OSTI Identifier:
530768
Resource Type:
Journal Article
Journal Name:
Journal of Clinical Endocrinology and Metabolism
Additional Journal Information:
Journal Volume: 81; Journal Issue: 4; Other Information: PBD: Apr 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; INSULIN; GENE MUTATIONS; RECEPTORS; GENETIC MAPPING; DIABETES MELLITUS; RISK ASSESSMENT; ETIOLOGY; PATIENTS; GENOTYPE; METABOLIC DISEASES; PHENOTYPE; WEIGHT; CODONS; AMINO ACIDS; RFLPS; STATISTICS; POLYMERASE CHAIN REACTION

Citation Formats

Sigal, R J, Doria, A, Warram, J H, and Krolewski, A S. Codon 972 polymorphism in the insulin receptor substrate-1 gene, obesity, and risk of noninsulin-dependent diabetes mellitus. United States: N. p., 1996. Web. doi:10.1210/jc.81.4.1657.
Sigal, R J, Doria, A, Warram, J H, & Krolewski, A S. Codon 972 polymorphism in the insulin receptor substrate-1 gene, obesity, and risk of noninsulin-dependent diabetes mellitus. United States. doi:10.1210/jc.81.4.1657.
Sigal, R J, Doria, A, Warram, J H, and Krolewski, A S. Mon . "Codon 972 polymorphism in the insulin receptor substrate-1 gene, obesity, and risk of noninsulin-dependent diabetes mellitus". United States. doi:10.1210/jc.81.4.1657.
@article{osti_530768,
title = {Codon 972 polymorphism in the insulin receptor substrate-1 gene, obesity, and risk of noninsulin-dependent diabetes mellitus},
author = {Sigal, R J and Doria, A and Warram, J H and Krolewski, A S},
abstractNote = {Because of the role of insulin receptor substrate-1 in insulin action, the insulin receptor substrate-1 gene is a candidate gene for noninsulin-dependent diabetes mellitus (NIDDM). Modest associations between NIDDM and a GGG-AGG single base substitution (corresponding to a glycine-arginine amino acid substitution) in codon 972 of the gene have been found, but none reached statistical significance. To examine further how large a proportion of NIDDM cases could be caused by the mutation, we performed a stratified analysis combining the results from the 6 earlier studies and those from our panel of 192 unrelated NIDDM subjects and 104 healthy controls. In addition, we looked for a possibility that the codon 972 mutation plays a role only in the presence of certain conditions. Genomic DNA samples obtained from NIDDM cases and healthy controls were genotyped using a PCR-restriction fragment length polymorphism protocol modified for genomic DNA. The GGG{r_arrow}AGG substitution was found in 5.7% of the diabetic subjects (11 of 192) and 6.9% of the controls (7 of 104). The difference between groups was not statistically significant, and it was not different from the results of other studies. The Mantel-Haenszel summary odds ratio across all studies was 1.49 (P < 0.05; 95% confidence intervals, 1.01-2.2). This summary odds ratio is consistent with a small proportion of NIDDM cases ({approximately}3%) being caused by the mutation. Exploratory subgroup analyses on our panel suggested a clustering of NIDDM, the codon 972 mutation, and overweight, raising the hypothesis that the mutation may predispose to NIDDM only in the presence of excess body weight. 9 refs., 2 tabs.},
doi = {10.1210/jc.81.4.1657},
journal = {Journal of Clinical Endocrinology and Metabolism},
number = 4,
volume = 81,
place = {United States},
year = {1996},
month = {4}
}