The TT Genotype of the MTHFR 677C>T Polymorphism Increases Susceptibility to Premature Coronary Artery Disease in Interaction with Some of the Traditional Risk Factors

Abstract

Background: The presence of several risk factors (genetic and non-genetic) has greater impact on the risk of premature coronary artery disease (CAD) than single risk factor. Objective: The aim of the study was to establish possible relations between genotypes and alleles of 677C>T polymorphism of MTHFR gene and some traditional risk factors e.g. elevated levels of lipid parameters and smoking in development of premature CAD. Methods: The groups comprised 152 patients with angiographically documented premature CAD (aged 42.9 ± 5.5) and 121 age-matched blood donors (aged 42.3 ± 6.5) were studied. The MTHFR 677C>T polymorphism was genotyped with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results: Patients with TT genotype who simultaneously smoked had increased risk of premature CAD compared to non-smoking cases with CC genotype (OR = 24.62). We also found that individuals with TT genotype and elevated LDL-cholesterol (LDL-chol.) level had significantly higher risk of CAD (OR = 9.92) than individuals with normal LDL-chol. level and CC genotype. Conclusions: The present study shows that simultaneous presence of MTHFR TT genotype and smoking or elevated levels of LDL-chol. influences the risk of premature CAD. This findings give interesting contribution to gene-environment interaction problem that may have clinical implications in the future.

Keywords

• Coronary artery disease
• Polymorphism
• MTHFR
• Lipids
• Traditional risk factors