Abstract
This study aimed to investigate whether the single nucleotide polymorphism C677T (rs1801133) of the methylene-tetrahydrofolate reductase (MTHFR) gene was associated with the risk of coronary artery disease (CAD) and circulating homocysteine (Hcy) levels in Tunisian population. 310 angiografically diagnosed CAD patients and 210 controls were enrolled in this study. The MTHFR C677T (rs1801133) polymorphism was genotyped, and the Hcy concentrations were measured. The severity of CAD was evaluated using the Gensini scoring system. Compared to the CC genotype, the TT genotype confers a higher risk for CAD severity with an OR = 9.07 and 95% CI = 3.78–21.8. The T allele was the predisposing allele for CAD and that it was probably associated with CAD severity. The area under the ROC curve for Hcy was 0.764 (95% CI 0.660 to 0.868, p = 0.001). The receiver operating characteristics curve (ROC) for Hcy showed its useful prediction of CAD. Hcy levels were not significantly associated with CAD severity expressed by Gensini Score (GS). The MTHFR C677T (rs1801133) polymorphism influences circulating Hcy levels. The MTHFR C677T polymorphism and hyperhomocysteinemia could have an important role in the prediction of the presence and not the severity expressed by GS of CAD.
Highlights
Homocysteine (Hcy) was known to be an independent risk factor for cardiovascular disease observed even in very young patients with extremely high serum Hcy concentrations
The main findings in this study were the elevation of Hcy levels influenced by the C677T polymorphism of the methylene-tetrahydrofolate reductase (MTHFR) gene in coronary artery disease (CAD) patients
These results suggest that the C677T polymorphism could be associated with increased susceptibility to develop CAD in Tunisian population
Summary
Homocysteine (Hcy) was known to be an independent risk factor for cardiovascular disease observed even in very young patients with extremely high serum Hcy concentrations. The transsulfuration pathway consists in the reaction of Hcy with serine catalysed by cystathionine b-synthase using vitamin B6 as a cofactor This reaction leads to the formation of Cystathionine which is converted into cysteine. Previous studies have shown that TT variants of MTHFR C677T polymorphism have been associated with elevated serum Hcy concentrations and severity of coronary lesions suggesting its important role as coronary artery disease (CAD) marker[7]. Several studies have suggested that HHcy can cause CAD, the association between Hcy and the severity of coronary lesions, in patients with acute coronary syndrome (ACS), has rarely been reported. It has been suggested that MTHFR C677T gene polymorphism may influence the association between Hcy levels and CAD occurrence risk[7]. As secondary objective we investigated the association between severity of CAD, MTHFR C677T polymorphism and its serum levels in a Tunisian population
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