Deletion Polymorphism in the Angiotensin-converting Enzyme Gene as a Thrombophilic Risk Factor after Hip Arthroplasty

Abstract

SummaryDespite 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.

Gene Polymorphisms of the Renin-Angiotensin System and Bleeding Complications of Warfarin: Genetic-Based Machine Learning Models

“…A recent meta-analysis including 39 case–control studies showed that ACE I/D polymorphism was significantly associated with intracranial hemorrhage, especially among Asians [ 13 ]. Although some studies have described the DD genotype as a potent thrombophilic factor [ 26 , 27 ], several studies have reported that D allele carriers of ACE have increased risk of hemorrhagic stroke [ 28 ] and blood loss after hip surgery [ 29 ], which is also consistent with our results.…”

Association of the ACE and AGT gene polymorphisms with global disparities in COVID-19-related deaths

“…Previous studies have reported a correlation between ACE polymorphisms and susceptibility to acute respiratory distress syndrome (ARDS) [8]. The deletion allele (D), defined as a D/D genotype, results in elevated expression and activity of ACE [9], mediating ARDS and mortality risk [8], increased obesity [10], thrombophilia [11], hypertension [12], and cardiovascular diseases [13]. Interestingly, the development of high blood pressure and cardiovascular disorders are common comorbidities in patients infected with SARS-CoV-2, and correlate with susceptibility to hospitalization and mortality [14][15][16][17].…”

The Effect of Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on the Severity and Death Rate of COVID-19 in Iranian Patients

“…It could be more sensibly justi ed since the spread, pathogenicity and mortality of SARS-CoV-2 can be attributed to several predisposing factors in population (Singhal 2020). Furthermore, the genetic variants of ACE have been already con rmed to be associated with the prognosis of some non-infectious lung diseases such as asthma (Gao et (Philipp et al 1998), as well as increased mortality in acute respiratory distress syndrome (ARDS) (Marshall et al 2002). Recent ndings have shown that all these clinical conditions are related to more aggressive type of COVID-19 (Wiersinga et al 2020).…”