title: Examination of two genetic polymorphisms within the renin-angiotensin system: no evidence for an association with nephropathy in IDDM.
abstract: Premature cardiovascular disease is common in insulin-dependent diabetic (IDDM) patients who develop diabetic nephropathy. Genetic polymorphism within the renin-angiotensin system has been implicated in the aetiology of a number of cardiovascular disorders; these loci are therefore candidate genes for susceptibility to diabetic renal disease. We have examined the angiotensin converting enzyme insertion/deletion polymorphism and angiotensinogen methionine 235 threonine polymorphism in a large cohort of Caucasian patients with IDDM and diabetic nephropathy. Patients were classified as having nephropathy by the presence of persistent dipstick positive proteinuria (in the absence of other causes), retinopathy and hypertension (n = 242). Three groups were examined for comparison: ethnically matched non-diabetic subjects (n = 187); a geographically defined cohort of newly diagnosed diabetic patients (n = 341); and IDDM patients with long duration of disease (> 15 years) and no evidence of overt nephropathy (n = 166). No significant difference was seen in distribution of angiotensin converting enzyme or angiotensinogen genotypes between IDDM patients with nephropathy and recently diagnosed diabetic subjects (p = 0.282 and 0.584, respectively), nor the long-duration non-nephropathy diabetic subjects (p = 0.701 and 0.190, respectively). We conclude that these genetic loci are unlikely to influence susceptibility to diabetic nephropathy in IDDM in the United Kingdom.
authors.affiliation: Department of Medicine, University of Birmingham, Birmingham Heartlands Hospital, UK.
authors.forename: T A
authors.initials: TA
authors.lastname: Chowdhury
authors.forename: M J
authors.initials: MJ
authors.lastname: Dronsfield
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: S L
authors.initials: SL
authors.lastname: Gough
authors.forename: S P
authors.initials: SP
authors.lastname: Gibson
authors.forename: A
authors.initials: A
authors.lastname: Khatoon
authors.forename: F
authors.initials: F
authors.lastname: MacDonald
authors.forename: B R
authors.initials: BR
authors.lastname: Rowe
authors.forename: D B
authors.initials: DB
authors.lastname: Dunger
authors.forename: J D
authors.initials: JD
authors.lastname: Dean
authors.forename: S J
authors.initials: SJ
authors.lastname: Davies
authors.forename: J
authors.initials: J
authors.lastname: Webber
authors.forename: P R
authors.initials: PR
authors.lastname: Smith
authors.forename: P
authors.initials: P
authors.lastname: Mackin
authors.forename: S M
authors.initials: SM
authors.lastname: Marshall
authors.forename: D
authors.initials: D
authors.lastname: Adu
authors.forename: P J
authors.initials: PJ
authors.lastname: Morris
authors.forename: J A
authors.initials: JA
authors.lastname: Todd
authors.forename: A H
authors.initials: AH
authors.lastname: Barnett
authors.forename: A J
authors.initials: AJ
authors.lastname: Boulton
authors.forename: S C
authors.initials: SC
authors.lastname: Bain
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics*; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011336:Probability; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A