title: A polymorphism in the angiotensin II type 1 receptor gene has different effects on the risk of diabetic nephropathy in men and women.
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.
  
  
  CONCLUSIONS
  We conclude that the AGTR1 gene may be associated with increased risk of diabetic nephropathy in men with type 1 diabetes.
authors.affiliation: Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden. anna.mollsten@pediatri.umu.se
authors.forename: Anna
authors.initials: A
authors.lastname: Möllsten
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vionnet
authors.forename: Carol
authors.initials: C
authors.lastname: Forsblom
authors.forename: Maija
authors.initials: M
authors.lastname: Parkkonen
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Groop
mesh_terms: D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000235:genetics*; D005060:Europe; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*
chemical_list: D044140:Receptor, Angiotensin, Type 1