Methylenetetrahydrofolate reductase gene polymorphism and its association with coronary artery disease

Abstract

CONTEXT AND OBJECTIVE: Obstructive coronary artery disease (CAD) is characterized by the deposition of atherosclerotic plaque on the coronary artery wall. Its manifestations depend on interactions between environmental and genetic risk factors. The aim of this work was to analyze the frequency of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in patients with CAD and its association with plasma homocysteine levels. Risk factors for CAD were also evaluated. DESIGN AND SETTING: Retrospective with blind quantitative analysis, at Hospital de Base, Faculdade de Medicina de São José do Rio Preto. METHODS: One hundred and twenty-seven individuals were studied. All completed a questionnaire to analyze risk factors for CAD. MTHFR polymorphism was investigated by restriction fragment length analysis and correlated with the number of affected arteries and degree of arterial obstruction determined by coronary cineangiography, and with plasma homocysteine levels measured by liquid chromatography/sequential mass spectrometry. RESULTS: Smoking (p = 0.02) and high-density lipoprotein cholesterol (p = 0.01) were associated with CAD. The C allele was the most prevalent in patients (0.61) and controls (0.66). There was no correlation between MTHFR/C677T polymorphism and plasma homocysteine levels. However, in patients with the TT genotype there was a correlation with the prevalence of coronary obstruction greater than 95% (p = 0.02) and the presence of two affected arteries (p = 0.04). CONCLUSIONS: The TT genotype is associated with coronary artery obstruction greater than 95% and the presence of two affected arteries. This confirms the relationship between genetic variants in specific patient subgroups and cardiovascular diseases.

Genetic polymorphisms involved in folate metabolism and concentrations of methylmalonic acid and folate on plasma homocysteine and risk of coronary artery disease

“…Polymorphism MTHFR C677T results in thermolability CAD coronary artery disease, SD standard deviation, Hcy homocysteine, MMA methylmalonic acid and enzyme activity reduction, contributing to increase the Hcy concentrations [26]. In the present study, the MTHFR C677T polymorphism was not associated with increased Hcy concentrations, as also reported in other studies with CAD individuals [27,28]. Other investigations showed increased Hcy concentration in carriers of the MTHFR 677TT genotype compared to the other genotypes; however, polymorphism MTHFR C677T was not associated with the development of CAD [25,29,30].…”

“…However, in line with our observations, Meisel et al [27] did not find a significant influence of the haplotypes MTHFR C677T and A1298C on the Hcy concentrations of CAD individuals. Furthermore, the haplotypes MTHFR A1298C and MTHFR C677T did not present any relation with the presence or the severity of CAD [28], just as in our study.…”

Homocysteine and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Tunisian patients with severe coronary artery disease

“…It was also suggested that C677T polymorphism, independent of altered homocysteine levels, was associated with CAD [27], while others suggested that hyperhomocysteinemia independent of the C677T genotype was linked with increased CAD risk [16,17,28,29], thus highlighting the contribution of other factors in inducing hyperhomocysteinemia in precipitating CAD. These apparently conflicting findings may be reconciled by is differences in ethnicity [13,16,25,26], relatively small sample size [13,17,27] coupled with the failure to control for confounding factors by some of these studies.…”

Variabilidade genética MTHFR no desenvolvimento da doença arterial coronária

“…Em DAC, o alelo polimórfico foi observado significantemente mais freqüente nos pacientes em relação aos controles [10][11][12][13][14]25 . Em estudo brasileiro, o polimorfismo foi associado à gravidade da doença, mas não apresentou distribuição significantemente diferente entre pacientes com e sem DAC 26 .…”