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ANALYSIS OF ASSOCIATION OF VITAMIN K EPOXIDE REDUCTASE COMPLEX SUBUNIT 1 (VKORC1) GENE HAPLOTYPES WITH ISCHEMIC ATHEROTHROMBOTIC STROKE

Аuthors: Ye. I. Dubovyk, V. Yu. Harbuzova,  A. V. Ataman

Pages: 546–554

Abstract

Introduction. Ischemic atherothrombotic stroke (IAS) is a multifactorial disease which development is determined by environmental and genetic factors. In recent years, a large number SNPs of various potential candidate-genes have been investigated to establish their association with IAS. However, haplotype analysis is considered more effective than single nucleotide polymorphism analysis to search for genetic determinants of widespread diseases or human features. Thus, the purpose of the present study was the conduction of a case-control study on representatives of the North-Eastern region of Ukraine in order to assess the possible association of vitamin K epoxide reductase complex subunit 1 (VKORC1) gene haplotypes with IAS.
Materials and methods. The study group included 170 unrelated Ukrainian patients with a mean age of 64.7 ± 0.73 years who had IAS. The control group consisted of 124 individuals with the absence of cardio-vascular pathologies. VKORC1 promoter G-1639A (rs9923231) and first intron C1173T (rs9934438) polymorphisms genotyping was performed using PCR-RFLP (polymerase chain reaction with following restriction fragment length polymorphism analysis) method. Most statistical analyses were performed using Statistical Package for Social Science software (SPSS, version 17.0, Chicago, IL, USA). Linkage disequilibrium (LD) and haplotype frequencies were analyzed by Arlequin (version 3.1, Bern, University of Berne, Switzerland). All statistical tests were two-sided, P <0.05 was considered significant.
Results. The data obtained in present work demonstrated that VKORC1 G-1639A but not C1173T polymorphism was associated with IAS in Ukrainian population. It has been shown that the risk for IAS in patients with A/A and G/A genotypes was higher than for individuals with G/G genotype (OR = 1.905; Р = 0.009). Haplotype analysis demonstrated, that -1639G/1173T and -1639A/1173C haplotypes frequencies in stroke subjects was significant higher than in matched control (OR = 3.813, P = 0.010 and OR = 2.189, P = 0.011, respectively). In contrast, -1639G/1173C haplotype frequency was higher in the control group (OR = 0.548, P < 0.001). Frequency of -1639A/1173T haplotype in both groups was similar (P = 0.218).
Conclusion. VKORC1 -1639G/1173T and -1639A/1173C haplotypes is related to increased risk for IAS, while -1639G/1173C is a protective factor for IAS in Ukrainian population.
Keywords: VKORC1, gene polymorphism, haplotype, ischemic stroke.

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