Deletion polymorphism in the angiotensin-converting enzyme gene as a thrombophilic risk factor after hip arthroplasty

Despite thromboprophylaxis, deep vein thrombosis is a common complication o f major orthopedic surgery. Predisposing genetic risk factors are unknown. In this case-control study, we investigated the association of the insertio n (I)/deletion (D) angiotensin converting enzyme (ACE) gene polymorphism. F actor V Leiden (R506Q) mutation, and 5,10 methylenetetrahydrofolate reducta se (MTHFR) gene polymorphism with post-operative venous thrombosis in 85 pa tients who underwent elective total hip arthroplasty. The odds of a thrombo tic event following hip surgery among subjects with the DD genotype of the ACE gene was increased more than 10-fold compared to subjects with the II g enotype (odds ratio 11.7 [95% confidence interval 2.3-84.5]); it was increa sed 5-fold in subjects with the ID genotype compared to the II genotype (od ds ratio 5.0 [95% confidence interval 1.1-34.9]). Mean plasma ACE level in control subjects not on ACE inhibitors at the time of study (n = 43) was lo west in persons homozygous for the I allele (18.9 +/- 7.95 U/l), intermedia te in patients with the ID genotype (31.6 +/- 10.8 U/l) and highest in subj ects homozygous for the D allele (44.0 +/- 7.14 U/l). Mean plasma ACE level among cases was higher (33.0 U/l, n = 25) than among controls (29.4 U/l, n = 43) but this difference was not statistically significant. Neither the F actor V Leiden mutation nor MTHFR gene polymorphism increased the risk of t hrombosis following hip replacement. These results demonstrate that the I/D ACE gene polymorphism is a potent risk factor for thrombosis in subjects u ndergoing total hip arthroplasty.