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

Nephrol Dial Transplant. 2013 Dec;28(12):3031-4. doi: 10.1093/ndt/gft325. Epub 2013 Sep 26.

Abstract

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 m(2)) 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 m(2), 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.

Keywords: gene polymorphism; insulin-resistance; kidney dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Creatinine / blood
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Europe / epidemiology
  • Female
  • Genotype
  • Glomerular Filtration Rate
  • Humans
  • Insulin Receptor Substrate Proteins / genetics*
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • Prevalence

Substances

  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Creatinine