title: Association between angiotensin-converting enzyme gene polymorphisms and diabetic nephropathy: case-control, haplotype, and family-based study in three European populations.
abstract: Angiotensin 1-converting enzyme gene (ACE) is a risk factor for diabetic nephropathy (DN) in patients with type 1 diabetes. The selection of this candidate gene is supported by cross-sectional and follow-up studies, but no convincing family-based studies are available. Recruited were 1057 patients (with DN: persistent albuminuria with or without renal failure) and 1127 control subjects (long-standing [> or =15 yr] normoalbuminuric patients with type 1 diabetes) in Denmark, Finland, and France and 532 family trios that were composed of 244 trios with DN probands and 288 trios with non-DN probands. Five ACE polymorphisms were studied. In the case-control analysis, the rs1800764-C, rs4311-T, Insertion/deletion (I/D or rs1799752)-D, rs4366-G, and rs12449782-G alleles were associated with an increased risk for DN, homogeneously across populations, with allelic odds ratios of 1.11 (95% confidence interval 1.00 to 1.22), 1.18 (1.04 to 1.33), 1.13 (1.02 to 1.23), 1.10 (0.99 to 1.20), and 1.12 (1.01 to 1.23), respectively. Haplotype analysis further demonstrated that the haplotype defined by the D, rs4366_G and rs12449782_G alleles was associated with a greater risk for DN. Even though no significant allelic overtransmission to DN or non-DN probands was detected, the family-based study provided consistent results with the case-control analysis. In a large case-control study, it was shown that the ACE polymorphisms were associated with DN; these findings were not confirmed in a family-based association study. This study population is suitable to search for additional candidate genes for DN.
authors: CHU de Poitiers, Department of Diabetology, Poitiers University Hospital, Poitiers, France. s.hadjadj@chu-poitiers.fr
authors: Samy
authors: S
authors: Hadjadj
authors: Lise
authors: L
authors: Tarnow
authors: Carol
authors: C
authors: Forsblom
authors: Gbenga
authors: G
authors: Kazeem
authors: Michel
authors: M
authors: Marre
authors: Per-Henrik
authors: PH
authors: Groop
authors: Hans-Henrik
authors: HH
authors: Parving
authors: François
authors: F
authors: Cambien
authors: David A
authors: DA
authors: Tregouet
authors: Ivo G
authors: IG
authors: Gut
authors: Alexandre
authors: A
authors: Théva
authors: Dominique
authors: D
authors: Gauguier
authors: Martin
authors: M
authors: Farrall
authors: Roger
authors: R
authors: Cox
authors: Fumihiko
authors: F
authors: Matsuda
authors: Mark
authors: M
authors: Lathrop
authors: Nathalie
authors: N
authors: Hager-Vionnet
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D007703:Peptidyl-Dipeptidase A