Abstract
Many epidemiological studies have reported an association between hemostatic factors and risk of both coronary and peripheral artery diseases. Using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis, we investigated the association between coronary artery disease and polymorphisms in the methylenetetrahydrofolate reductase ( MTHFR C677T and A1298C), prothrombin (G20210A), and factor V (A4070G) genes. We screened these gene variants in 174 subjects who had undergone coronary angiography - 115 patients with patent coronary artery disease (grade 3 vessel disease, i.e. , significant coronary stenosis), and 59 healthy controls with grade 0 vessel disease. The analysis of our data did not show any statistically significant association between coronary artery disease (CAD) and the investigated polymorphisms.
genetic polymorphism; coronary disease; MTHFR gene; prothrombin gene; Factor V gene
GENETICS
MTHFR, prothrombin and Factor V gene variants in Turkish patients with coronary artery stenosis
Müge Caner1
Rifat Bircan2
Deniz Sevinç1
Fehime Benli3
A. Ilter Güney4
Nuri Kurtoglu5
1Department of Medical Biology, Maltepe University, School of Medicine, Istanbul, Turkey
2Department of Molecular Biology, Namik Kemal University, Faculty of Arts and Sciences, Tekirdag, Turkey
3Department of Biochemistry, Maltepe University, School of Medicine, Istanbul, Turkey
4Department of Medical Biology, Marmara University, School of Medicine, Istanbul Turkey
5Department of Cardiology, Safak Hospital, Istanbul, Turkey
Many epidemiological studies have reported an association between hemostatic factors and risk of both coronary and peripheral artery diseases. Using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis, we investigated the association between coronary artery disease and polymorphisms in the methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), prothrombin (G20210A), and factor V (A4070G) genes. We screened these gene variants in 174 subjects who had undergone coronary angiography - 115 patients with patent coronary artery disease (grade 3 vessel disease, i.e., significant coronary stenosis), and 59 healthy controls with grade 0 vessel disease. The analysis of our data did not show any statistically significant association between coronary artery disease (CAD) and the investigated polymorphisms.
This case-control study involved 174 individuals who had undergone coronary angiography. The patient group included 115 subjects with grade 3 vessel disease, i.e., significant coronary stenosis, and the control group was formed by 59 subjects with grade 0 vessel disease. The distributions of patients and controls according to gender, family history of coronary disease, and comorbidities are shown in Table 1. No statistically significant associations between gender or traditional risk factors and the presence of coronary artery stenosis were detected, except in relation to hypercholesterolemia.
Genomic DNA was extracted from venous blood samples by the standard phenol-chloroform method. Polymorphisms in the candidate genes were investigated by polymerase chain reaction followed by restriction fragment length polymorphism analysis (PCR-RFLP) as follows: C677T (Frosst et al., 1995) and A1298C (van der Put et al., 1998) of the MTHFR gene, G20210A of the prothrombin gene (Poort et al., 1996), and A4070G of the Factor V-Leiden gene (Alhenc-Gelas et al., 1999). No differences were found between patients and controls in terms of genotype and allele frequencies in relation to the four genetic polymorphisms studied (Table 2).
Our results are consistent with those of Yilmaz et al. (2006), who did not find an association between MTHFR C677T and increased risk for CAD in Turkish patients either. In contrast to these results, two other studies showed a significant increase in the frequency of the MTHFR C677T polymorphism among patients with CAD (Almawi et al., 2004, in a sample from the Bahrain population; Ghazouani et al., 2008, in Tunisians). However, concerning the MTHFR A1298C polymorphism, Ghazouani et al. (2008) did not find a significant difference between patients and controls, in line with the present study.
The carrier frequency of the factor V-Leiden (G1691A) and prothrombin G20210A gene polymorphisms did not differ between patients and controls in the study of Almawi et al. (2004), in accordance with our results. Similarly, Baykan et al. (2001) did not find an increased frenquency of factor V-Leiden in patients presenting with CAD either.
In conclusion, although the results concerning the association of the MTHFR C677T polymorphism with CAD are still controversial, the factor V-Leiden and prothrobin G20210A polymorphisms do not seem to confer an increased risk for CAD in the different populations studied.
References
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Received: February 1, 2008; Accepted: May 14, 2008
Müge S. Caner. School of Medicine, Maltepe University, Feyzullah Caddesi n. 39 Maltepe 34845 Istanbul, Turkey. E-mail: mugecaner@yahoo.co.uk.
Publication Dates
-
Publication in this collection
19 Nov 2008 -
Date of issue
2008
History
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Accepted
1405 -
Received
1022
