Association of Methylenetetrahydrofolate Reductase Gene Polymorphism With Carotid Atherosclerosis Depending on Smoking Status in a Japanese General Population

Abstract

Background and Purpose-The association of the methylenetetrahydrofolate reductase gene (MTHFR) with carotid atherosclerosis remains inconsistent. This may be due to small sample size and inappropriate analysis. We investigated the association of C677T/MTHFR with blood pressure and carotid atherosclerosis in a Japanese general population. Methods-Subjects (30 to 89 years of age; 1693 women, 1554 men) who gave informed consent were randomly selected from a general population in Suita, Japan. MTHFR genotypes were determined by TaqMan polymerase chain reaction. Carotid atherosclerosis was evaluated by high-resolution ultrasonography with atherosclerotic indexes of intimal-medial thickness (IMT), maximum IMT in the common carotid artery (CCA), plaque score, and stenosis (Ͼ50%). Results-Age-adjusted diastolic blood pressure was significantly higher in women with the TT genotype than in those with the CC genotype. In a recessive model (CCϩCT versus TT), all adjusted odds ratios for hypertension and Ͼ50% stenosis in women were 1.42 and 3.42 (95% confidence intervals, 1.01 to 1.99 and 1.23 to 9.53), respectively. In women, maximum IMT in CCA for smokers with the TT genotype was significantly higher than for smokers with the CC genotype and nonsmokers with the TT genotype (PϽ0.05). Conclusions-Our study suggests that the MTHFR TT genotype is a risk factor for hypertension and carotid stenosis in women. Significant interactions between C677T/MTHFR and smoking on maximum IMT in CCA were observed in women but not in men. Smoking cessation for subjects with the TT genotype is important in the prevention of cerebrovascular disease.

D919G polymorphism of methionine synthase gene is associated with blood pressure response to benazepril in Chinese hypertensive patients

“…The MTHFR gene C677T polymorphism, which is located in the predicted catalytic domain of the MTHFR enzyme, was found to be associated with a decreased enzyme activity and an elevated plasma Hcy level (Frosst et al 1995). Individuals carrying the mutant T allele with a higher plasma Hcy level might also have a higher blood pressure (Inamoto et al 2003). Thus, the T allele of the MTHFR C677T polymorphism and the 919G allele of the MTR D919G polymorphism seem to have conflicting effects in blood pressure response to benazepril.…”

Riboflavin status, MTHFR genotype and blood pressure: current evidence and implications for personalised nutrition

“…Although there is strong evidence linking this polymorphism with hypertension, a number of observational studies have reported conflicting or inconclusive results. Many of the studies that failed to detect significant associations used small sample sizes or suffered possible selection bias (93,(95)(96)(97)(98)(99) . Some studies have reported a gender specific association; one large population study in >3000 Japanese individuals reported that the MTHFR 677C T polymorphism was associated with a 42 % increased risk of hypertension in women but not in men (96) .…”

“…Many of the studies that failed to detect significant associations used small sample sizes or suffered possible selection bias (93,(95)(96)(97)(98)(99) . Some studies have reported a gender specific association; one large population study in >3000 Japanese individuals reported that the MTHFR 677C T polymorphism was associated with a 42 % increased risk of hypertension in women but not in men (96) . In contrast, in a Spanish cohort, the TT genotype was found to be a significant predictor of hypertension in men but not in women, however, only 26 % of the sample were females (100) .…”

Genetic basis of hypertension for the development of tailored medicine

“…25 The C677T polymorphism of the methyleneteterahydrofolate reductase (MTHFR) gene was also found to be significantly correlated with hyperhomocysteinemia and carotid atherosclerosis in Japanese women, and the significance increased when the women smoked. 26 Thus, in individuals who are genetically sensitive to ROS, a recommendation to cease smoking and to modify lifestyle, or drug administration to reduce oxidative stress, should be given. Recent pharmacological studies have shown that the combination of pioglitazone and candesartan exerts more beneficial effects on hypertensive cardiovascular damage by increasing the suppression of ROS.…”