These data provide evidence for a strong association between type 2 diabetes and the G1057D common genetic variant of IRS-2, which appears to be protective against type 2 diabetes in a codominant fashion.
The Gly1057Asp polymorphism was not associated with insulin resistance or impaired insulin secretion in Finnish subjects with normal glucose tolerance (n = 295) or impaired glucose tolerance (n = 38).
The Gly1057Asp polymorphism was not associated with insulin resistance or impaired insulin secretion in Finnish subjects with normal glucose tolerance (n = 295) or impaired glucose tolerance (n = 38).
Polymorphisms in the genes encoding the insulin receptor substrate (IRS) proteins, IRS-1 (Gly(972)Arg) and IRS-2 (Gly(1057)Asp), influence susceptibility to type 2 diabetes.
These results suggest that the IRS-2 Gly(1057)Asp polymorphism influences blood glucose levels in nondiabetic white and African-American women with PCOS.
We investigated the significance of Gly1057Asp and Leu647Val insulin receptor substrate (IRS)-2 polymorphisms in two Italian cohorts comprising 186 glucose-tolerant subjects and 240 subjects with type 2 diabetes from the Lazio region (i.e. representative of central Italy), and 123 glucose-tolerant subjects from the Sicily region (i.e. representative of south Italy).
Logistic regression analysis with nine haplotypes in the whole sample revealed that obesity was associated with haplotype H3, with P<0.025, an odds ratio (OR) of 1.9 and a 95% confidence interval (CI) of 1.1-3.4, or pairs 3/3 ( P<0.005, OR=8.7, CI=1.9-40.1) and 3/4 ( P<0.023, OR=2.5, CI=1.1-5.6), all containing the the Gly1057Asp allelic variant of IRS2, whereas controls were associated with H5 and H6 ( P<0.02, OR=0.2, CI=0.01-0.81).
These data indicate that IRS2 is an influential gene in severe obesity and glucose intolerance in this population, whereas gene-based haplotypes of IRS2 have revealed heterogeneity in the behaviour of the Gly1057Asp mutation in relation to insulin resistance.
We investigated the significance of Gly1057Asp and Leu647Val insulin receptor substrate (IRS)-2 polymorphisms in two Italian cohorts comprising 186 glucose-tolerant subjects and 240 subjects with type 2 diabetes from the Lazio region (i.e. representative of central Italy), and 123 glucose-tolerant subjects from the Sicily region (i.e. representative of south Italy).
These data indicate that IRS2 is an influential gene in severe obesity and glucose intolerance in this population, whereas gene-based haplotypes of IRS2 have revealed heterogeneity in the behaviour of the Gly1057Asp mutation in relation to insulin resistance.
The aim of our study was to investigate whether common polymorphisms in the genes regulating the early insulin signalling pathway (insulin; A-23T, insulin-like growth factor 1 receptor [IGF-1R]; GAG1013GAA, plasma cell membrane glycoprotein 1 [PC-1]; K121Q, insulin receptor substrate [IRS-1]; G972R, insulin receptor substrate 2 [IRS-2]; G1057D and phosphatidylinositol 3-kinase p85 alpha [PI3K]; M326I) affect the weight change and development of Type 2 diabetes in the Finnish Diabetes Prevention Study.
A commonly occurring nucleotide polymorphism of the insulin-receptor substrate 2 (IRS-2) gene at amino acid 1057 from Glycine to Asparaginic acid (G1057D) was recently shown to be a determinant of insulin sensitivity in both glucose-tolerant individuals and those with type 2 diabetes.
We evaluated the effect of polymorphisms in four insulin-related genes (G972R in IRS1, G1057D in IRS2, a CA repeat in IGFI and an A/C polymorphism at -202 of IGFBP3) on the risk of microsatellite instability and KRAS2 and TP53 mutations in a population-based set of 1788 cases of colon cancer and 1981 controls.
We evaluated the effect of polymorphisms in four insulin-related genes (G972R in IRS1, G1057D in IRS2, a CA repeat in IGFI and an A/C polymorphism at -202 of IGFBP3) on the risk of microsatellite instability and KRAS2 and TP53 mutations in a population-based set of 1788 cases of colon cancer and 1981 controls.
When these three SNPs were examined as a haplotype, only the haplotype that included the G allele of rs2289046 was associated with breast cancer (odds ratio = 0.76, 95% confidence interval = 0.63-0.92 for TGC versus CAT).
When these three SNPs were examined as a haplotype, only the haplotype that included the G allele of rs2289046 was associated with breast cancer (odds ratio = 0.76, 95% confidence interval = 0.63-0.92 for TGC versus CAT).