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.
However, the evidence for a link between the IRS2 (rs2289046) variant and risk of CRC dependent on the BMI of the subjects, requires confirmation in subsequent studies with greater sample size.
In conclusion, in our elderly subjects the presence of the allelic variant Gly1057Asp of IRS2 gene was associated to the degree of insulin resistance assessed by HOMA index and with EpiF thickness, independently from the extent of obesity, suggesting its contribution to global cardiometabolic risk.
IRS2 1057G/A combined with the INSR His 1085 His polymorphism increased the odds ratio of drug resistance in TLE (P=0.011, OR=2.263, 95% CI: 1.208-4.239).
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).
No statistically significant differences in the prevalence of IRS-1 Gly972Arg or IRS-2 Gly1057Asp polymorphisms or any combination of both were observed between controls and PCOS patients (P > 0.02).
Our findings suggest that IRS-1 Gly972Arg polymorphism is associated with PCOS in the Caucasian ethnicity, and IRS-2 Gly1057Asp polymorphism is correlated with PCOS in the Asian ethnicity.
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.