Impact of Thrombomodulin Polymorphism -33G>A on Acute Myocardial Infarction Risk and Circulating Inflammatory Markers

Abstract

Background: There is increasing evidence that thrombomodulin (THBD) polymorphisms, along with inflammatory markers [i.e., C-reactive protein (CRP), fibrinogen, albumin], may increase the risk of acute myocardial infarction (AMI). The aim of the study was to investigate the role of the THBD -33G>A polymorphism (rs1042579) as a marker of AMI risk and to correlate it with serum levels of inflammatory markers.

Methods: Case-control study of 277 AMI patients and 329 healthy controls. A binary logistic regression analysis was performed to evaluate the association between the parameters studied and AMI risk.

Results: The frequencies of genotypes AA, GA, and GG of the THBD -33G>A polymorphism were 31.4%, 45.5%, and 23.1% in patients and 21.6%, 44.1%, and 34.3% in controls. A significant association was found between the AA genotype of the THBD -33G>A polymorphism (AA: OR = 2.011, 95% CI 1.561-3.074, P < .001) or A allele (A: OR = 1.725, 95% CI 1.493-2.510, P < .001) and AMI risk. A backward stepwise logistic regression method combining AMI status as the dependent variable and conventional risk factors (age, smoking, arterial hypertension (HTA), diabetes, dyslipidemia, CRP, albumin, fibrinogen, serum angiotensin converting enzyme (ACE) activity, serum malondialdehyde, conjugated dienes, glutathione peroxidase, cardiac troponin-I (cTnI) and THBD AA genotype) as independent variables showed that the most predictive risk factors for AMI were smoking, HTA, albumin, fibrinogen, CRP, ACE activity, cTnI, and the THBD AA-genotype with odds ratios of 2.942, 2.203, 2.352, 1.323, 1.652, 1.014, 2.105, and 3.781 respectively. The AA genotype was associated with increased diastolic blood pressure, CRP, ACE activity, and albumin levels.

Conclusions: The study shows that the THBD -33G>A polymorphism should be included in the stratification of AMI risk.

Figure 1.

Scatterplot illustrating the Pearson’s rank correlations between (1) Albumin and (a) Fibrinogen (r = −0.391; P = .001), (b) serum ACE activity (r = 0.057; P = .401), (c) cTnI (r = 0.047; P = .486), (d) CRP (r = −0.511; P = .001) and (2) Fibrinogen and (e) GPx (r = −0.031; P = .624), (f) serum ACE activity (r = −0.020; P = .754), (g) cTnI (r = −0.043; P = .497), (h) CRP (r = 0.217; P = .001) in AMI patients.