An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and common carotid atherosclerosis

Abstract

Plasma homocysteine (Hcy) concentration has been shown to be influenced by a mutation in the gene coding methylenetetrahydrofolate reductase (MTHFR). Although plasma Hcy is related to atherosclerotic disorders, conflicting results have been reported about the association between MTHFR gene polymorphism and sclerotic lesions of the common carotid arteries. The effect of agegene interaction on carotid arterial remodeling was investigated in elderly subjects with several risk factors for atherosclerosis. We evaluated sclerotic lesions of the common carotid arteries by ultrasonography in 326 patients (mean age Ϯ standard deviation, 73 Ϯ 12 years) and studied relations among the known risk factors for atherosclerosis, including MTHFR gene polymorphism and its interactions with age and sex. Of the 326 subjects studied, 136 had MTHFR genotype CC, 136 genotype CT, and 54 genotype TT. The three groups did not differ with respect to background factors such as age, history of cigarette smoking, blood pressure, lipids or uric acid, or in the incidence of atherosclerotic diseases. Spearman's rank correlation revealed a significant relationship between gender, age, Brinkman index, systolic blood pressure, triglycerides, HDL-cholesterol (HDL-C), uric acid, and MTHFR gene polymorphism. Multiple regression analysis using intimamedia complex thickness (IMT) as a criterion variable and risk factors, including MTHFR gene polymorphism as explanatory variables showed that MTHFR gene polymorphism (P ϭ 0.039) was a significant independent explanatory variable for IMT, along with gender (male) (P Ͻ 0.001), age (P Ͻ 0.001), systolic blood pressure (SBP) (P ϭ 0.047), total cholesterol (T-C) (P Ͻ 0.001), and HDL-C (P Ͻ 0.001). Furthermore, a general linear model analysis revealed that interaction between age and MTHFR gene polymorphism was significantly associated with IMT, independently of age, SBP, T-C, and HDL-C in male subjects. However, age-gene interaction was not observed in female subjects. The findings of the present study confirm an association between MTHFR gene polymorphism and common carotid atherosclerosis in the Japanese population and further support the role of risk factor-gene interaction in common carotid atherosclerosis.

Effect of folic acid treatment on carotid intima-media thickness of patients with coronary disease

“…There are studies that describe a positive relation, but measurement of folate was not done in all of them [13,14,28]. In a recent meta-analysis a positive association of coronary disease with MTHFR 677TT mutation has been described when folate status was low or normal, but not when it was high [10].…”

WITHDRAWN: Association of homocysteine-metabolizing enzyme gene polymorphisms and lipid profiles: an investigation of a geneenvironment interaction

“…Several other studies also confirmed that MTHFR C677T is a key genetic determinant of lipid profiles. For example, evidence that the MTHFR gene polymorphism is an important independent contributor to TC and HDL-C was found by Kawamoto et al [19], and Pitsavos et al reported that TC and TG are statistically different across MTHFR genotypes [20]. Another functional polymorphism in the MTR gene is A2756G, located at position 919 of the protein and resulting in a substitution of glycine for aspartic acid [21].…”

The Independent and Joint Association of Blood Pressure, Serum Total Homocysteine, and Fasting Serum Glucose Levels With Brachial-Ankle Pulse Wave Velocity in Chinese Hypertensive Adults

“…41,42) However, different results for the association between MTHFR C677T genotype and atherosclerosis have been reported. Woodside 43) showed that arterial PWV is not associated with MTHFR genotype in a healthy young population, while Kawamoto 44) proved that MTHFR C677T genotype was associated with carotid atherosclerosis in an elderly Japanese population. Our study demonstrates that increased Hcy levels, rather than MTHFR C677T genotype, are associated with the development of baPWV in hypertensive patients.…”