title: A disease haplotype for advanced nephropathy in type 2 diabetes at the ACE locus.
abstract: Previous investigations of the ACE gene as a susceptibility factor for diabetic nephropathy have primarily focused on its insertion/deletion (Ins/Del) polymorphism. In a departure from these earlier studies, we used three tagging markers (A-5466C, T-3892C, and Ins/Del) at the ACE locus to test for disease haplotype associations. A case-control study design was used where case subjects were type 2 diabetic patients with advanced diabetic nephropathy, as indicated by the presence of proteinuria or chronic renal failure/end-stage renal disease, while control subjects were normoalbuminuric, despite >6 years of diabetes. None of the individual markers showed significant disease association when considered on their own. However, haplotype analyses revealed a near doubling in the prevalence of the A.T.D risk haplotype in case subjects (0.136) compared with control subjects (0.075) (P = 0.009), thus providing first evidence for a disease haplotype for advanced diabetic nephropathy at the ACE locus.
authors.affiliation: Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore.
authors.forename: Daniel P K
authors.initials: DP
authors.lastname: Ng
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Placha
authors.forename: Serena
authors.initials: S
authors.lastname: Choo
authors.forename: Kee-seng
authors.initials: KS
authors.lastname: Chia
authors.forename: James H
authors.initials: JH
authors.lastname: Warram
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Krolewski
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D017354:Point Mutation; D044465:White People / Q000235:genetics
chemical_list: C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A