P272Genetic aspects of thrombus formation in left atrial appendage in patients with atrial fibrillation

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Abstract

Purpose

To study the role of genetic polymorphisms of cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex subunit 1 (VKORC1) and plasminogen activator inhibitor -1 (PAI-1) in left atrial appendage (LAA) thrombus formation in patients with atrial fibrillation.

Methods

Studied were 100 patients with coronary heart disease and permanent atrial fibrillation, mean age was 65.4 ± 5.4 years. Patients were divided into two groups according to results of transesophageal echocardiography: group 1 included 50 patients with LAA thrombosis, group 2 — 50 patients without LAA thrombosis who were age and sex matched. We evaluated genetic polymorphisms Arg144Cys and Ile359Leu of CYP2C9, C1173T and G3730A of VKORC1 and -675 5G/4G of PAI-1.

Results

The frequency of CC, CT and TT genotypes of VKORC1 C1173T among all the patients was 28%, 54% and 18%, GG, GA and AA genotypes of VKORC1 G3730A — 38%, 52% and 10%, 5G/5G, 5G/4G and 4G/4G genotypes of PAI-1 -675 5G/4G — 42%, 48% and 10% respectively. The frequency of CYP2C9*1/*1, *1/*2 and *1/*3 genotypes was 69%, 18% and 13% respectively. In our study, no genotypes CYP2C9*2/*2 and CYP2C9*3/3 were observed. Genotypes distribution fulfilled expectations of Hardy-Weinberg equilibrium.

Results

Patients of the 1 group had 4G allele of PAI-1 -675 5G/4G 10% more frequently (p=0.005) and genotype CC of VKORC1 C1173T 35% more frequently (p=0.01) than patients of the 2 group. Correlations between CC genotype of VKORC1 C1173T and LAA thrombosis (r=0.46; p=0.01) and between 4G allele of PAI-1 -675 5G/4G and LAA thrombosis (r=0.35; p=0.01) were observed. The odds ratio for LAA thrombosis in patients with CC genotype of VKORC1 C1173T was 3.2 (95% CI 1.1 to 7.8) (p=0.02) and in patients with 4G allele of PAI-1 -675 5G/4G - 4.2 (95% CI 1.5 to 8.6) (p=0.02).

Conclusion

CC genotype of VKORC1 C1173T and 4G allele of PAI-1 -675 5G/4G are associated with LAA thrombosis in patients with permanent atrial fibrillation.

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