Methylenetetrahydrofolate Reductase Genotypes and Early-Onset Coronary Artery Disease

Mager, Aviv; Lalezari, Shadan; Shohat, Tamar; Birnbaum, Yochai; Adler, Yehuda; Magal, Nurit; Shohat, Mordechai

doi:10.1161/01.cir.100.24.2406

Cited by 70 publications

(35 citation statements)

References 24 publications

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“…Our findings support the view that TT MTHFR is an important risk factor for premature CHD in Europeans. 15,18,31 We found that elevated plasma homocysteine concentrations in Indian Asian, compared with European, white controls, were explained by their low folate and B 12 concentrations. In contrast, homocysteine concentrations in Indian Asian and European white CHD patients, compared with controls, were only partially accounted for by differences in age, creatinine, vitamin status, and MTHFR genotype.…”

Section: Discussionmentioning

confidence: 75%

“…More recent data show a significantly higher frequency of homozygosity for the MTHFR 677T mutation in patients with early-onset CHD than in patients with later-onset CHD or in control subjects. 31 The odds ratio for CHD in the young has been reported as 2.4 (95% CI, 1.2 to 4.7). 31 In the present study, we found that the prevalence of homozygosity for MTHFR 677T was higher in European white cases with onset of CHD before the age of 50 years compared with controls.…”

Section: Discussionmentioning

confidence: 99%

“…31 The odds ratio for CHD in the young has been reported as 2.4 (95% CI, 1.2 to 4.7). 31 In the present study, we found that the prevalence of homozygosity for MTHFR 677T was higher in European white cases with onset of CHD before the age of 50 years compared with controls. Our findings support the view that TT MTHFR is an important risk factor for premature CHD in Europeans.…”

Section: Discussionmentioning

confidence: 99%

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Methylenetetrahydrofolate Reductase 677 C → T Mutation and Coronary Heart Disease Risk in UK Indian Asians

Chambers

Ireland

Thompson

et al. 2000

ATVB

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Abstract-Plasma homocysteine concentrations are elevated in UK Indian Asians and may contribute to twice as many coronary heart disease (CHD) deaths in this group compared with European whites. The mechanisms underlying elevated homocysteine concentrations among Indian Asians are not well understood. In this study, we have investigated the extent to which the methylenetetrahydrofolate reductase (MTHFR) 677 C3T mutation accounts for elevated plasma homocysteine and increased CHD risk in Indian Asians compared with European whites. We investigated 454 male cases (with myocardial infarction or angiographically proven CHD: 224 Indian Asians, 230 European whites) and 805 healthy male controls (381 Indian Asians, 424 European whites). Fasting homocysteine concentrations, MTHFR 677 C3T genotype, and conventional CHD risk factors were measured. The prevalence of homozygous MTHFR 677T in Indian Asian controls was less than one third that in European white controls (3.1% versus 9.7%, PϽ0.001). In Indian Asians, the TT MTHFR genotype was not associated with homocysteine concentrations and was not present in any of the Asian controls with hyperhomocysteinemia (Ͼ15 mol/L). In contrast, among European whites, the TT MTHFR genotype was strongly related to elevated plasma homocysteine concentrations and was found in 27% of the European controls with hyperhomocysteinemia. Elevated homocysteine in Indian Asian compared with European white controls was accounted for by their reduced levels of B vitamins but not by the MTHFR 677T genotype. However, neither the TT MTHFR genotype nor B vitamin levels explained the elevated homocysteine concentrations in CHD cases compared with controls. TT MTHFR was not a risk factor for early-onset CHD in Indian Asians (odds ratio, 0.5; 95% confidence interval, 0.1 to 2.4; Pϭ0.39), unlike in European whites (odds ratio, 2.1; 95% confidence interval, 1.1 to 4.1; Pϭ0.02). We conclude that the MTHFR 677T mutation does not contribute to elevated plasma homocysteine concentrations or increased CHD risk in Indian Asians compared with European whites. Our results suggest that novel genetic defects and/or environmental factors influence homocysteine metabolism in Indian Asians residing in the United Kingdom.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Methylenetetrahydrofolate Reductase 677 C → T Mutation and Coronary Heart Disease Risk in UK Indian Asians

Chambers

Ireland

Thompson

et al. 2000

ATVB

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“…6 Other studies also support the notion that hyperhomocysteinemia is considered an independent risk factor for vascular disease: it has been demonstrated in the Physicians' Health Study,I in the European Concerted Action Project,I') and recently in a study that demonstrated that the homozygosity for the 677C) T mutation of methylenetetrahydrofolate reductase is common and is associated with an increased risk of premature CAD in this population. 20 The role of homocysteine in atherogenesis and progression of vascular disease is unknown. Several mechanisms were suggested, among them procoagulant effects.…”

Section: Discussionmentioning

confidence: 99%

Homocysteine levels in patients with risk factors for atherosclerosis

Blum

Lupovitch

Khazim

et al. 2001

Clinical Cardiology

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SummaryBLtckgrOund: Abundant epidemiological evidence has demonstrated that the presence of mild to moderate hyperhomocysteinemia is an independent risk factor for atherosclerosis in the coronary, cerebral, and peripheral vasculature, and for vascular disease, including coronary disease. It has been demonstrated that plasma total homocysteine level is a strong predictor of mortality in patients with angiographically confirmed coronary artery disease.Hvpothesis: The study was undertaken to determine the extent of homocysteine levels in patients without documented coronary artery disease, but with at least one risk factor for atherosclerosis.Methods: Fasting blood samples were collected prospectively from 160 consecutive patients (50 women and 1 10 men, mean age 65 f 7 years) who had at least one risk factor for atherosclerosis, but had no documented coronary artery disease. Homocysteine levels were measured by an immunoassay method.Resulrs: Of the patients studied, 78 (48.75%) with at least one risk factor for atherosclerosis had high homocysteine levels; 62 patients had mild hyperhomocysteinemia ( 15-30 pmol/l); and 16 patients had moderate hyperhomocysteinemia (3C100 pnolil). Conclusions: Our data suggest that hyperhomocysteinemia is highly prevalent in patients with risk factors for atherosclerosis. Homocysteine level (an independent convertible risk factor to atherosclerosis) should be measured routinely in patients with risk factors for atherosclerosis and treated appropriately.

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“…Ambos os polimorfismos do gene MTHFR foram considerados fatores de risco para DAC 7,8,9,10 . A associação do polimorfismo MTHFR C677T com DAC foi confirmada por alguns estudos, nos quais a prevalência de portadores do alelo alterado foi maior no grupo DAC em relação aos controles [10][11][12][13][14] por outro lado, outros trabalhos não confirmam tal associação 15,16,17 .…”

Section: Introductionunclassified

Variabilidade genética MTHFR no desenvolvimento da doença arterial coronária

Biselli¹,

Guerzoni²,

Goloni-Bertollo³

et al. 2009

Rev. Assoc. Med. Bras.

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ResumoObjetivO. Concentração elevada de homocisteína (Hcy) é considerada um fator de risco para doença arterial coronária (DAC). Alterações genéticas da enzima metilenotetrahidrofolato redutase (MTHFR), envolvida no metabolismo da Hcy, podem reduzir sua termolabilidade contribuindo para o desenvolvimento de lesões ateroscleróticas. O objetivo deste estudo foi investigar a relação entre os polimorfismos MTHFR C677T e A1298C e a presença, extensão e gravidade da DAC. MétOdOs. Foram avaliados 175 pacientes com DAC, confirmada por angiografia e 108 indivíduos sem DAC (grupo controle). O polimorfismo MTHFR C677T foi investigado por reação em cadeia da polimerase (PCR) seguida de digestão enzimática. A genotipagem do polimorfismo MTHFR A1298C foi realizada pela técnica de PCR alelo-específica. ResultadOs. A frequência do alelo alterado MTHFR 677C foi de 0,38 no grupo DAC e 0,37 no grupo controle. Em relação ao alelo polimórfico MTHFR 1298C, a frequência foi de 0,22 e 0,27, respectivamente. As distribuições genotípicas MTHFR C677T e A1298C não diferiram em relação ao número de artérias lesadas (P > 0,05). Também não foi observada relação entre o polimorfismo para MTHFR C677T e grau de obstrução arterial coronária (P > 0,05), assim como MTHFR A1298C (P > 0,05). COnClusãO. Nossos resultados não demonstraram associação entre os polimorfismos MTHFR A1298C e MTHFR C677T e presença, extensão ou gravidade da DAC.Unitermos: Doença arterial coronária. Polimorfismos genéticos. Enzima MTHFR.

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Methylenetetrahydrofolate Reductase Genotypes and Early-Onset Coronary Artery Disease

Abstract: Homozygosity for the 677C-->T mutation of MTHFR is common and is associated with an increased risk of premature CAD in this population.

Cited by 70 publications

References 24 publications

Methylenetetrahydrofolate Reductase 677 C → T Mutation and Coronary Heart Disease Risk in UK Indian Asians

Methylenetetrahydrofolate Reductase 677 C → T Mutation and Coronary Heart Disease Risk in UK Indian Asians

Homocysteine levels in patients with risk factors for atherosclerosis

Variabilidade genética MTHFR no desenvolvimento da doença arterial coronária

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