The IRS1 G972R polymorphism and glomerular filtration rate in patients with type 2 diabetes of European ancestry

Background. In Mexican Americans, the IRS1 G972R polymorphism (rs1801278) has been associated to such a marked reduction in glomerular filtration rate (GFR) (i.e. β = -8.3 mL/ min/1.73 m2) to be considered a major determinant of kidney function. Methods. This was a cross-sectional study to investigate whether a similarly strong effect can also be observed among individuals of European ancestry. We investigated a total of 3973 White patients with type 2 diabetes. Standardized serum creatinine was measured by the modified kinetic Jaffè reaction and estimated GFR (eGFR) calculated by the modification diet renal disease (MDRD) formula; rs1801278 was genotyped by TaqMan assay. Results. No significant association was observed, with R972 carriers showing only a modestly, not significant, lower eGFR level as compared with other subjects (β = -1.82 mL/min/ 1.73 m2, P = 0.086). Conclusions. Our data indicate that IRS1 G972R is not a strong determinant of GFR in diabetic patients of European ancestry as in Mexican Americans. Since we had 100% power to detect the previously reported association, the risk our finding is a false negative one is minimal. Kidney dysfunction predisposes to end-stage renal disease both in the general population and in diabetic patients. Several pieces of evidence indicate that low glomerular filtration rate (GFR) is heritable, thus suggesting it is under the influence of genetic determinants. A number of genetic variations known to affect whole body insulin sensitivity have been associated with reduced GFR in diabetic patients. In contrast to what was reported in Mexican Americans, IRS1 G972R polymorphism has no a strong effect on eGFR) in patients with type 2 diabetes of European ancestry.