title: Angiotensin-converting enzyme (ACE) inhibition in type 2, diabetic patients-- interaction with ACE insertion/deletion polymorphism.
abstract: Angiotensin-converting enzyme (ACE) insertion(I)/deletion (D) polymorphism may modify the effect of inhibition of the renin-angiotensin-aldosterone system (RAAS) on survival and cardiorenal outcomes in type 2, diabetes. A consecutive cohort of 2089 Chinese type 2 diabetic patients with mean (+/- standard deviation) age of 59.7 +/- 13.1 years were genotyped for this polymorphism by polymerase chain reaction method and were followed prospectively for a median period of 44.6 (interquartile range: 23.7, 57.5) months. Clinical outcomes, including all-cause mortality, cardiovascular and renal end points, were examined. The frequency for I allele was 67.1 and 32.9% for D allele, with observed genotype frequencies of 45.8, 42.6, and 11.6% for 3, DI and DD, respectively. ACE DD polymorphism was an independent predictor for renal end point with hazard ratio (HR) (95% confidence interval) of 1.72 (1.16, 2.56), but not for cardiovascular end point or mortality. After controlling for confounding factors, including ACE I/D genotype, the usage of RAAS inhibitors was associated with reduced risk of mortality (HR 0.34 (0.23, 0.50)) and renal end point (HR 0.55 (0.40, 0.75)). On subgroup analysis, the beneficial effects on survival (II vs DI vs DD: HR 0.29 (0.16, 0.51) vs 0.25 (0.14, 0.46) vs 1.33 (0.41, 4.31)) and renoprotection (II vs DI vs DD: 0.52 (0.30, 0.90) vs 0.43 (0.25, 0.72) vs 0.95 (0.43, 2.12)) were most evident in II and DI carriers. In conclusion, inhibition of RAAS was associated with reduced risk of mortality and occurrence of renal end point in Chinese type 2 diabetic patients. These benefits were most evident among II and DI carriers.
authors.affiliation: Department of Medicine and Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong. wingyeeso@cuhk.edu.hk
authors.forename: W Y
authors.initials: WY
authors.lastname: So
authors.forename: R C W
authors.initials: RC
authors.lastname: Ma
authors.forename: R
authors.initials: R
authors.lastname: Ozaki
authors.forename: P C Y
authors.initials: PC
authors.lastname: Tong
authors.forename: M C Y
authors.initials: MC
authors.lastname: Ng
authors.forename: C S
authors.initials: CS
authors.lastname: Ho
authors.forename: C W K
authors.initials: CW
authors.lastname: Lam
authors.forename: C C
authors.initials: CC
authors.lastname: Chow
authors.forename: W B
authors.initials: WB
authors.lastname: Chan
authors.forename: A P S
authors.initials: AP
authors.lastname: Kong
authors.forename: J C N
authors.initials: JC
authors.lastname: Chan
mesh_terms: D000368:Aged; D000483:Alleles; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D044466:Asian People; D015331:Cohort Studies; D016001:Confidence Intervals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012084:Renin-Angiotensin System / Q000235:genetics; D016019:Survival Analysis
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A