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ASSOCIATION ANALYSIS OF THE ARG325GLN POLYMORPHISM γ-GLUTAMYLCARBOXYLASE GENE WITH ACUTE CORONARY SYNDROME IN PATIENTS WITH NORMAL AND HIGH BLOOD PRESSURE

Authors: Parkhomenko O.M.,Dosenko V.Ye.,  Ataman O.V.,  Garbuzova V.Yu.

Pages: 132-140

Abstract

       

Introduction. Vitamin K-dependent γ-glutamylcarboxylase (GGCX) is the integral transmembrane protein, which catalyzes the posttranslational carboxylation of glutamic acid to γ-carboxyglutamic acid molecules in the vitamin K-dependent proteins that are synthesized in the liver (clotting factors II, VII, IX, X, protein S, C, and Z), and in other tissues (osteocalcin, protein S, Gas6 and four transmembrane proteins: PRGP1, PRGP2, TmG3, and TmG4). Taking into account importance of coagulant status in the development of coronary disorders, polymorphism of GGCX gene may be associated with them. The data in literature concerning these issues are limited and inconsistent, and absent for Slavic populations.

Purpose. Our aim was to establish the frequency of allelic variants of the GGCX gene for Arg325Gln polymorphism in patients with acute coronary syndrome (ACS), who has normal and high blood pressure.

Materials and Methods. We used venous blood of 118 patients with ACS (22 % women and 78 % men) aged 40 to 73 years (mean age 55.9 ± 0.89 years) who were hospitalized in the cardiology department of Sumy City Clinical Hospital № 1. The control group consisted of 234 patients. Definition of Arg325Gln polymorphism (rs699664) of GGCX gene was performed using PCR with the following restriction fragment length analysis of the allocation of them by electrophoresis in agarose gel. Restriction endonuclease XmnI was used for restriction analysis. Statistical analysis was performed using the software package SPSS-17. Thus the significance of differences was determined by the χ2-criterion. The value of P < 0.05 was considered as significant.

Results. Using the χ2-Pearson criterion did not reveal association between the Arg325Gln polymorphism of GGCX gene and the development of ACS. Distribution of different types of genotype between patients with ACS and healthy patients did not differ statistically significantly. However, using logistic regression led to the conclusion of the association of polymorphism of the 8th exon of the GGCX gene with acute coronary syndrome. In carriers of minor allele (Gln/Gln) ACS risk twice that of homozygotes for the major allele (Arg/Arg).

The obtained data on the performance of systolic (SBP), diastolic (DBP), pulse (PBP) and average (ABP) blood pressure in patients in the control group and patients with ACS with different genotypes for the polymorphism Arg325G in GGCX gene indicated that all four types of BP did not differ in carriers of different genotypes inside the control group and in patients with ACS. A comparison between the groups

revealed that for the studied polymorphism in members of Arg/Gln and Arg/Arg genotype and DBP and ABP values were significantly higher in patients with ACS than in control.

A somewhat different pattern was revealed when the analysis was conducted among females. Women with ACS homozygotes for the minor allele (Gln/Gln), only DBP; in homozygotes for the major allele (Arg/Arg) DBP and ABP, while heterozygotes (Arg/Gln) and SAT were also higher when compared with almost healthy individuals. As for men, the effect of blood pressure on the development of ACS was insufficient. SBP value in the comparison group did not significantly differ among carriers of different genotypes. DBP was higher in patients with genotype Arg/Gln and Gln/Gln, and PAT – with Arg/Arg, and ABP – with Gln/Gln, suffering from ACS.

Among persons with high blood pressure significant difference in the ratio of genotypes (Arg/Arg, Arg/Gln, Gln/Gln) existed between main and control groups. In the group with ACS, it accounted for 20.8, 56.9, 22.2 %, and in control – 38.4, 49.3, 12.3% (P = 0.045). Thus, among the people with high blood pressure with genotype Gln/Gln, risk of ACS development was greater. Logistic regression confirmed the conclusion: the minor allele homozygotes had risk of the ACS 3.3 times greater than that of homozygotes for the major allele.

Conclusion: In homozygotes for the minor allele (Gln/Gln), the risk of ACS was twice higher than in homozygotes for the major allele (Arg/Arg).

Among representatives of Arg/Gln and Arg/Arg genotype, DBP and ABP parameters were significantly higher in patients with ACS than in control.

Among people with high blood pressure with genotype Gln/Gln, risk of development of ACS was 3.3 times higher than that of homozygotes for the major allele (Arg/Arg).

Key wordsallelic polymorphism, blood pressure, acute coronary syndrome, γ-glutamylcarboxylase.

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