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 of major orthopedic surgery. Predisposing genetic risk factors are unknown. In this case-control study, we investigated the association of the insertion (I)/deletion (D) angiotensin converting enzyme (ACE) gene polymorphism, Factor V Leiden (R506Q) mutation, and 5,10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with post-operative venous thrombosis in 85 patients who underwent elective total hip arthroplasty. The odds of a thrombotic 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 genotype (odds ratio 11.7 [95% confidence interval 2.3-84.5]); it was increased 5-fold in subjects with the ID genotype compared to the II genotype (odds 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 lowest in persons homozygous for the I allele (18.9+/-7.95 U/l), intermediate in patients with the ID genotype (31.6+/-10.8 U/l) and highest in subjects 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 Factor V Leiden mutation nor MTHFR gene polymorphism increased the risk of thrombosis following hip replacement. These results demonstrate that the I/D ACE gene polymorphism is a potent risk factor for thrombosis in subjects undergoing total hip arthroplasty.
Philipp
C S
CS
Division of Hematology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08904, USA.
Dilley
A
A
Saidi
P
P
Evatt
B
B
Austin
H
H
Zawadsky
J
J
Harwood
D
D
Ellingsen
D
D
Barnhart
E
E
Phillips
D J
DJ
Hooper
W C
WC
D020016:Activated Protein C Resistance / Q000453:epidemiology / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000925:Anticoagulants / Q000627:therapeutic use; D019644:Arthroplasty, Replacement, Hip; D002318:Cardiovascular Diseases / Q000453:epidemiology; D016022:Case-Control Studies; D015897:Comorbidity; D005165:Factor V / Q000032:analysis / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009515:New Jersey / Q000453:epidemiology; D009765:Obesity / Q000453:epidemiology; D016017:Odds Ratio; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D015995:Prevalence; D011655:Pulmonary Embolism / Q000453:epidemiology* / Q000209:etiology; D044469:Racial Groups / Q000235:genetics; D012307:Risk Factors; D017384:Sequence Deletion; D012907:Smoking / Q000453:epidemiology; D019851:Thrombophilia / Q000453:epidemiology* / Q000235:genetics; D020246:Venous Thrombosis / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control
D000925:Anticoagulants; C095381:factor V Leiden; D005165:Factor V; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007703:Peptidyl-Dipeptidase A