title: Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary heart disease in non-insulin-dependent diabetes mellitus.
abstract: Non-insulin-dependent diabetes mellitus (NIDDM) is considered a model of premature atherosclerosis with a strong genetic component. We have investigated the role of angiotensin-converting enzyme (ACE; EC 3.4.15.1) gene in 316 unrelated NIDDM individuals, 132 who had myocardial infarction or significant coronary stenoses and 184 with no history of coronary heart disease (CHD). A deletion-polymorphism in the ACE gene was recently reported to be associated with myocardial infarction especially in people classified as low risk. Here we report that the D allele of the ACE gene is a strong and independent risk factor for CHD in NIDDM patients. The D allele is associated with early-onset CHD in NIDDM, independently of hypertension and lipid values. A progressively increasing relative risk in individuals heterozygous and homozygous for the D allele was observed (odds ratios of 1.41 and 2.35, respectively; P < 0.007), suggesting a codominant effect on the cardiovascular risk. The percentage of CHD attributable to the ACE deletion allele was 24% in this NIDDM population. Identification of NIDDM patients carrying this putative CHD-susceptibility genotype would help early detection and treatment of CHD.
authors.affiliation: Centre d'Etude du Polymorphisme Humain, (Fondation Jean Dausset-CEPH), Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Ruiz
authors.forename: H
authors.initials: H
authors.lastname: Blanché
authors.forename: N
authors.initials: N
authors.lastname: Cohen
authors.forename: G
authors.initials: G
authors.lastname: Velho
authors.forename: F
authors.initials: F
authors.lastname: Cambien
authors.forename: D
authors.initials: D
authors.lastname: Cohen
authors.forename: P
authors.initials: P
authors.lastname: Passa
authors.forename: P
authors.initials: P
authors.lastname: Froguel
mesh_terms: D000483:Alleles; D003327:Coronary Disease / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D007703:Peptidyl-Dipeptidase A