Risk of venous thromboembolism associated with the insertion/deletion polymorphism in the angiotensin-converting enzyme gene

The circulating levels of angiotensin I-converting enzyme (ACE) are linked with a 287-base pair insertion/deletion (I/D) polymorphism at intron 16 of the ACE gene. Thus, the homozygous deletion (D/D genotype) could cause chro nic vasoconstriction, arterial hypertension and, possibly, coronary artery disease. Also, the increase in plasminogen activator inhibitor-1 level and impaired fibrinolysis were related with the D/D genotype. The D allele has been recently associated with venous thrombosis among African-American men as well as among patients that underwent elective total hip replacement. We assess the risk of venous thromboembolism (VTE) linked with each genotype of the I/D ACE gene polymorphism in a Caucasian population by means of a ca se-control study. We genotyped the ACE gene in a series of 148 patients age d 45.0 +/- 16.0 years (range, 11-80 years), objectively diagnosed in our ce ntre of deep-vein thrombosis or pulmonary embolism, and in 240 thrombosis-f ree subjects (25-75 years) from the same geographic area. The observed diff erence in D allele frequencies between patients (0.56) and controls (0.62) was nonsignificant overall; however, statistical significance (P = 0,05) wa s found by considering the recessive hypothesis (D/D versus I/D D + I/I) [o dds ratio (OR) = 0.64, 95% confidence interval (CI95) = 0.42-0.99]. The OR was 0.88 (CI95 = 0.51-1.53; P = 0.65) for the dominant hypothesis (D/D + I/ D versus I/I genotypes). The relative risk for the D allele was close to 1 for the dominant hypothesis, both considering gender and recurrent tendency ; however, it was protective in men regarding the recessive hypothesis (OR = 0,53, CI95 = 0.29-0.97, P = 0,04). The I/D ACE allele distribution was si milar among the 46 thrombophilic patients (antithrombin, protein C or prote in S deficiencies, factor V R506Q, factor II G20210A or lupus anticoagulant ). In conclusion, among (Spanish) Caucasians, this study does not support t he hypothesis that the deletion allele (D) of the ACE gene could be a signi ficant risk factor for VTE, being protective in men. (C) 2000 Lippincott Wi lliams & Wilkins.