The angiotensin-converting enzyme insertion/deletion polymorphism and serum levels of angiotensin-converting enzyme in venous thromboembolism

Abstract

The angiotensin-converting enzyme (ACE) has been suggested to affect blood coagulation and fibrinolysis. Results from literature on the role of the frequent insertion/deletion (I/D) polymorphism in the ACE gene in venous thromboembolism (VTE) are controversial. Only limited data on ACE serum levels inVTE exist. We determined the ACE I/D polymorphism by genotyping and ACE serum levels by an enzymatic assay in 100 high-risk patients with objectively confirmed recurrentVTE and at least one event of an unprovoked deep venous thrombosis or pulmonary embolism. One hundred twenty-five age- and sex-matched healthy individuals served as controls. ACE genotype frequencies were not significantly different between patients (DD: 26.0%, ID: 52.0%, II: 22.0%) and controls (DD: 29.6%, ID: 44.8%, II: 25.6%; p = 0.56). Neither individuals with ACE DD genotype nor those with ACE ID genotype had a higher risk for VTE in comparison to those with ACE II genotype (odds ratio and [95% confidence interval]: 1.0 [0.5-2.1] and 1.4 [0.7-2.6], respectively). Serum ACE levels (U/l) did not differ between patients (median = 25.25, 25th -75th percentile: 20.20-33.70) and controls (24.20, 17.85-34.50, p = 0.49). In the total population involved in the study the ACE DD genotype (n = 63: 36.00 [26.40-43.00]) was associated with higher ACE levels than the ACE ID genotype (n = 108: 24.10 [19.80-31.48], p < 0.001) and the ACE II genotype (n = 54: 19.35 [15.00-22.95], p < 0.001). In conclusion, we found a significant association of the ACE I/D polymorphism with ACE serum levels. However, neither the serum levels nor the I/D genotype were associated with VTE.

Polymorphisms in<i> ACE</i> and <i>ACTN3</i> Genes and Blood Pressure Response to Acute Exercise in Elite Male Athletes from Serbia

“…Namely, the ACE DD genotype is associated with higher levels of serum ACE (Ay et al 2007). A number of studies have confirmed that individuals with the DD genotype have a higher incidence of myocardial infarction and other cardiovascular disorders, and even sudden cardiac death (Gard 2010).…”

“…ACE gene, which contains 26 exons and 25 introns, is located on chromosome 17q23 (Tiret et al 1992). Although there are many identified polymorphic sites in ACE gene, some of which located in the coding regions of this gene, polymorphism rs4646994 defined by the presence (insertion, I allele), or the absence (deletion, D allele) of 287-base pair (bp) Alu fragment in intron 16 of the gene, is by far the best studied (Folland et al 2000;Ay et al 2007). This polymorphism, unlikely functional due to its location, can explain nearly a half of the inter-individual variation in production and activity of ACE, both in tissues and in the circulation.…”

Ischemic stroke in a young man with MTHFR A1298C and ACE I/D polymorphism

“…There is evidence that allele I of ACE gene is associated with lower ACE levels, whereas D allele is associated with increased ACE activity (10). According to the meta-analysis results performed by Zhang, the D allele of ACE I/D polymorphism is a low-penetrance susceptibility marker of ischemic stroke (9).…”

Gender association of the angiotensin-converting enzyme gene with ischaemic stroke

“…22,24,25 There is evidence that allele I of ACE gene is associated with lower ACE levels, whereas D allele is associated with increased ACE activity. 26,27 Few studies demonstrate genderrelated comparisons with genes, regarding multifactorial disorders as stroke, and refer to oestrogen receptor genes. 28,29 Regarding ACE gene, a limited number of studies demonstrate certain differences regarding gender, such as the higher levels of Ang-I and Ang-II in DD females in a series of healthy individuals 22 and the higher levels of renin and prorenin levels in DD women.…”