A polymorphism in the angiotensin II type 1 receptor gene has different effects on the risk of diabetic nephropathy in men and women

Mol Genet Metab. 2011 May;103(1):66-70. doi: 10.1016/j.ymgme.2011.01.004. Epub 2011 Jan 19.

Abstract

Background: The etiology of diabetic nephropathy depends partly on genetic factors. Elevated systemic and intraglomerular blood pressure and glomerular filtration rate, partly regulated by the renin-angiotensin system, increase the risk of diabetic nephropathy.

Methods: The present case-control study investigated the association of the rs5186 polymorphism, in the angiotensin II type 1 receptor gene (AGTR1), with diabetic nephropathy. The study included 3561 patients with type 1 diabetes from Denmark, Finland, France and Sweden. Microalbuminuria was defined as albumin excretion rate (AER) ≥20 to <200 μg/min or albumin concentration ≥30 to <300 mg/l (n=707), macroalbuminuria was defined as AER≥200 μg/min or ≥300 mg/l (n=1546), and patients with renal replacement therapy were also included in this group. The controls had >15 years diabetes duration, AER <20 μg/min or <30 mg/l, and no antihypertensive treatment (n=1308).

Results: AA genotype of the rs5186 polymorphism significantly increased the risk of diabetic nephropathy in male patients, OR=1.27 (95% CI=1.02-1.58), P=0.03, adjusted for age at diabetes onset, HbA1c, diabetes duration, smoking and country of origin. Among the women, there were no significant associations between rs5186 and diabetic nephropathy, OR=0.89 (0.71-1.11), P=0.30.

Conclusion: We conclude that the AGTR1 gene may be associated with increased risk of diabetic nephropathy in men with type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Case-Control Studies
  • Child
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetic Nephropathies / etiology*
  • Diabetic Nephropathies / genetics*
  • Europe
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Male
  • Polymorphism, Genetic / genetics*
  • Receptor, Angiotensin, Type 1 / genetics*

Substances

  • Receptor, Angiotensin, Type 1