Genetic Polymorphism of 5,10-Methylenetetrahydrofolate Reductase (MTHFR) as a Risk Factor for Coronary Artery Disease

Morita, Hiroyuki; Taguchi, Junichi; Kurihara, Hiroki; Kitaoka, Masao; Kaneda, Hideaki; Kurihara, Yukiko; Maemura, Koji; Minamino, Tohru; Ohno, Minoru; Yamaoki, Kazuhide; Ogasawara, Kunio; Aizawa, Tadanori; Suzuki, Shin; Yazaki, Yoshio

doi:10.1161/01.cir.95.8.2032

Cited by 300 publications

(211 citation statements)

References 31 publications

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“…With respect to MTHFR gene polymorphism, 136 had genotype CC, 136 genotype CT, and 54 genotype TT. The distribution of MTHFR genotypes was consistent with published data for Japanese subjects (Morita et al 1997) and was in agreement with the expected Hardy-Weinberg ratio (P ϭ 0.36). Among the three MTHFR genotypes, there were no differences in background factors, including age, history of cigarette smoking, blood pressure, lipids, and uric acid, or in the incidence of atherosclerotic diseases such as hypertension, diabetes mellitus, ischemic heart disease, or cerebral infarction (Table 1).…”

Section: Resultssupporting

confidence: 90%

“…There have been numerous genetic association studies of the MTHFR C677T variant, particularly in the homozygous state, which have shown both the presence (Arruda et al 1997;Cattaneo et al 1997;Christensen et al 1997;Kluijtmans et al 1997;Morita et al 1997) and absence (Anderson et al 1997;Legnani et al 1997;Ma et al 1996;Press et al 1999;Rees et al 1997;Schwartz et al 1997) of significant associations with such end points as coronary heart disease, myocardial infarction, thrombo-occlusive disease, and cerebrovascular disease. However, the relationship between elevated plasma Hcy concentration and the end points of vascular disease appears to be consistent, even in those studies that failed to show an association with the MTHFR C677T variant.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2001

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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.

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Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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

et al. 2001

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“…There have been reports of increased risk for cardiovascular disease in persons with the MTHFR C677T mutation (Morita et al 1997;Kang et al 1988Kang et al , 1991Gallagher et al 1996;Kluijtmans et al 1996). In one study, the presence of the MTHFR C677T mutation in a group of patients with venous thromboembolic disease in various parts of the body, mainly in deep large veins was examined (Arruda et al 1997).…”

Section: Discussionmentioning

confidence: 99%

“…A number of investigations have been done to identify whether the thermolabile mutant, MTHFR C677T causes an increased risk for cardiovascular disease. Some results suggest such a correlation (Morita et al 1997;Kang et al 1988Kang et al , 1991Gallagher et al 1996;Kluijtmans et al 1996), whereas others do not (Verhoef et al 1997;Anderson et al 1997;Ma et al 1996;Deloughery et al 1996;van Bockxmeer et al 1997;Christensen et al 1997;Wilcken et al 1996;Adams et al 1996;Brugada & Marian;1997). Arruda et al have shown that there is a correlation between homozygosity for the MTHFR C677T mutation and venous thromboembolic disease (Arruda et al 1997).…”

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confidence: 99%

Hyperhomocysteinemia and the MTHFR C677T mutation in central retinal vein occlusion

Larsson

Hultberg

Hillarp³

2000

Acta Ophthalmologica Scandinavica

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ABSTRACT.Background: Hyperhomocysteinemia is a factor that predisposes to thrombosis, and the C677T mutation in methylene-tetrahydrofolate reductase (MTHFR) is known to give increased plasma homocysteine. We wanted to investigate if these factors were overrepresented in a group of patients with central retinal vein occlusion. Methods: 116 patients with a history of central retinal vein occlusion were examined for the presence of hyperhomocysteinemia and the MTHFR C677T mutation. Results: Compared to the control groups, there was no significant increase, neither in plasma homocysteine nor in the frequency of the MTHFR C677T mutation in the patients. Even when we looked selectively at the young patients, age less than 50 years, no difference could be detected. Conclusion: It seems that neither hyperhomocysteinemia nor the MTHFR C677T mutation is an important risk factor for the aetiology of central retinal vein occlusion.

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“…TT MTHFR homozygotes are predisposed to increased plasma homocysteine levels, particularly in individuals with low folate [22,23]. Hyperhomocysteinemia has been implicated in premature vascular disease [24], venous thrombosis [25] and unexplained early pregnancy loss [23,26]. Hyperhomocysteinemia caused by the C677T polymorphism has been associated with coronary artery disease, venous thrombosis and complications of pregnancy i.e.…”

Section: Introductionmentioning

confidence: 99%

Methylenetetrahydrofolate Reductase C677T Polymorphism and Recurrent Pregnancy Loss Risk in Asian Population: A Meta-analysis

Rai

2016

Ind J Clin Biochem

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The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene was implicated to be associated with thrombophilia due to its role in catalyzing the formation of 5-methylenetetrahydrofolate, a co-substrate for the conversion of homocysteine to methionine. Several case-control studies were investigated MTHFR C677T polymorphism as risk for recurrent pregnancy loss (RPL). These studies rendered contradictory results, some indicating that the polymorphism is associated with the risk of RPL whereas others concluded there is no association. To shed light on these inconclusive findings, a meta-analysis of all available studies published from Asian population relating the C677T polymorphism to the risk of RPL was conducted. The following electronic databases were searched without language restrictions: PubMed, Google Scholars, Elsevier and Springer Link up to December, 2015. Meta-analysis was performed using MetaAnalyst and Mix version 1.7. Meta-analysis results suggested that MTHFR C677T polymorphism contributed to the increased RPL risk in Asian population using all five genetic models (for T vs. C: OR 1.35, 95 % CI 1.09-1.68, p = 0.009; for TT ? CT vs. CC: OR 1.44, 95 % CI 1.14-1.82, p = 0.006; for CT vs. CC: OR 1.39, 95 % CI 1.07-1.8, p = 0.01; for TT vs. CC: OR 1.79, 95 % CI 1.23.2.6, p = 0.007; for TT vs. CT ? CC: OR 1.61, 95 % CI 1.02-2.56, p = 0.04). In conclusion, this meta-analysis demonstrates a strong association between the MTHFR C677T variant and RPL in Asian population and raising the importance of the use of folate in its treatment and prevention.

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Genetic Polymorphism of 5,10-Methylenetetrahydrofolate Reductase (MTHFR) as a Risk Factor for Coronary Artery Disease

Cited by 300 publications

References 31 publications

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

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

Hyperhomocysteinemia and the MTHFR C677T mutation in central retinal vein occlusion

Methylenetetrahydrofolate Reductase C677T Polymorphism and Recurrent Pregnancy Loss Risk in Asian Population: A Meta-analysis

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