Relation Between Folate Status, a Common Mutation in Methylenetetrahydrofolate Reductase, and Plasma Homocysteine Concentrations

Jacques, Paul F.; Bostom, Andrew G.; Williams, Roger R.; Ellison, R. Curtis; Eckfeldt, John H.; Rosenberg, Irwin H.; Selhub, Jacob; Rozen, Rima

doi:10.1161/01.cir.93.1.7

Cited by 1,297 publications

(834 citation statements)

References 8 publications

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“…The finding of an interaction effect between smoking and MTHFR(C677T) genotype has not been reported previously. A suboptimal plasma folate status among smokers (Piyathilake et al, 1994;Cafolla et al, 2000;O'Callaghan et al, 2002) might explain the observed interaction, as plasma folate has been shown to interact with MTHFR(C677T) genotype (Jacques et al, 1996b;Brattstrom et al, 1998;Girelli et al, 1998;McQuillan et al, 1999;Dekou et al, 2001;Saw et al, 2001). The involvement of folate is further supported by another study in which smoking was reported to interact with the dietary intake of folate (De Bree et al, 2001b).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have showed that B-vitamin status is a major determinant of tHcy in the general population (Jacques et al, 1996b(Jacques et al, , 2002Hustad et al, 2000;Moat et al, 2003). Little attention has been given to the effect of overall dietary pattern regarding tHcy.…”

Section: Discussionmentioning

confidence: 99%

“…Persons homozygous for the mutant T-allele have higher tHcy concentrations than persons with CC and CT genotypes (Husemoen et al, 2003). Moreover, the MTHFR(C677T) polymorphism has been shown to modify the relation between B-vitamin intake and tHcy (Jacques et al, 1996a(Jacques et al, , 2002Hustad et al, 2000). Suboptimal vitamin status is associated with much higher tHcy concentrations in persons with the TT genotype than in persons with the CC or CT genotypes.…”

Section: Introductionmentioning

confidence: 99%

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Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype. Inter99 (7)

et al. 2004

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Objective: To examine the associations between various lifestyle factors-smoking habits, physical activity, dietary habits, coffee, tea, and alcohol consumption-and homocysteine (tHcy) in relation to MTHFR(C677T) genotype. Design: Cross-sectional population-based study. Setting: Residents of Copenhagen County, Denmark. Subjects: A random sample of 6457 men and women aged 30-60 years drawn from the Civil Registration System and invited to a health examination in 1999-2001. A total of 2788 participants were included in the statistical analysis. Main outcome measures: tHcy was measured using a Fluorescent Polarization Immuno Assay. MTHFR-genotype was determined by PCR and RFLP analysis. Information about lifestyle factors was obtained from a self-administered questionnaire. Results: Daily smoking, less healthy dietary habits, and coffee drinking were associated with elevated tHcy concentrations independent of other determinants. Wine consumption was related to tHcy in a J-shaped manner, whereas beer consumption was negatively associated with tHcy after multiple adjustments. Interaction was observed between smoking status and MTHFRgenotype, smoking status and sex, and beer consumption and age. The effect of smoking was more pronounced in persons with the TT genotype and in women. The effect of beer consumption was more pronounced at younger than at older ages. Conclusions: Smoking status, dietary habits, coffee intake, wine, and beer consumption were major lifestyle determinants of tHcy. Changes in these lifestyle factors may reduce tHcy concentrations, thereby lowering cardiovascular risk in the general population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype. Inter99 (7)

et al. 2004

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“…The MTHFR 677TT genotype confers a significant risk of hyperhomocysteinemia that is most pronounced in individuals with low folate [15,16] or low riboflavin [17] status. Interestingly, the MTHFR 677C>T polymorphism appears to have a sex-specific effect on homocysteine [18].…”

Section: Introductionmentioning

confidence: 99%

Evidence for sex differences in the determinants of homocysteine concentrations

Stanisławska-Sachadyn

Woodside

Brown

et al. 2008

Molecular Genetics and Metabolism

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A high homocysteine phenotype, often accompanied by low folate, is associated with several pathologies including cardiovascular disease and birth defects. This phenotype appears to be influenced by both genetic and environmental factors, which may act in a sex-dependent manner. The present analyses were undertaken to identify the determinants of homocysteine concentrations in young men and women, and are based on data from a cohort of young, reproductive age (20-26 years old) individuals in Northern Ireland. Multivariate modeling indicated that homocysteine concentrations are associated with red blood cell (RBC) folate, vitamin B 12 , MTHFR 677C>T genotype and smoking status in both males and females. However, the inter-relationships between these variables appear to differ between the sexes. Specifically, homocysteine levels in males were significantly associated with interactions between MTHFR 677C>T genotype and both RBC folate and smoking status. In contrast, homocysteine levels in females were significantly associated with interactions between smoking status and RBC folate. These results suggest that the characteristics of individuals who are at the highest risk for a high homocysteine phenotype differ for males and females. Among males, those with the MTHFR 677TT genotype appear to be at the highest risk and to be the most vulnerable to factors (e.g. smoking, low RBC folate) that are associated with homocysteine raising effects. Among females, smokers (regardless of MTHFR genotype) appear to be at the highest risk, and to be the most vulnerable to a single factor (i.e. RBC folate) that is associated with homocysteine raising effects.

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“…7 Homozygous MTHFR C677T mutations can cause mildly elevated homocysteine levels, but this effect is neutralised if there is a high folate content in the diet. 8 Thus, many patients homozygous for this abnormality have normal homocysteine levels. In contrast, most studies directly measuring homocysteine find high levels to be associated with RVO.…”

Section: Introductionmentioning

confidence: 99%

The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion

Dodson

Haynes

Starczynski

et al. 2003

Eye

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Retinal vein occlusion (RVO) is associated with hyperhomocysteinaemia and the antiphospholipid syndromeFdisorders known to contribute to both arterial and venous thrombosis. In both of these conditions and RVO, platelet activation occurs. Aspirin, not warfarin, is the most effective antithrombotic agent in RVO and, taken together, these observations suggest an important role for platelets in this common ocular thrombotic condition. Platelet glycoprotein Ia/IIa (GpIa/IIa) is an adhesion molecule mediating platelet-collagen interactions and is key to the initiation of thrombosis. Recently, the cellular density of this molecule was shown to be determined by two silent, linked polymorphisms (C807T/ G873A) within the GpIa/IIa gene. There is evidence that some of the resulting genotypes are associated with thrombo-embolic disease. This study therefore aimed to establish the prevalence of the GpIa/IIa polymorphisms and the three commonest hereditary thrombophilic disorders (prothrombin gene G20210A (PT) mutation, Factor V Leiden (FVL), and the thermolabile methylene tetrahydrofolate reductase C677T (MTHFR) mutation) in patients with RVO and normal controls. The GpIa/IIa polymorphisms and thrombophilic abnormalities were all identified using the polymerase chain reaction. Our results show that the frequency of the GpIa/IIa polymorphisms was similar in our normal control population to previously published series. Patients with RVO, however, had only a 10% (4/40) frequency of the lowest risk subtype (CC/GG) compared to 37.5% (15/40) in the control groupFP 0.0039.The incidence of the PT, FVL, and MTHFR thrombophilic mutations was not different between the two groups, but interestingly none of the 7/40 RVO cases with a PT, FVL, or MTHFR mutation had the low-risk GpIa/IIa genotype while all but one of the controls didFPo0.05. Thus, 17.5% of RVO patients harboured more than one prothrombotic abnormality. The principal difference between the RVO and control group was the very high incidence of the intermediate-risk GpIa/IIa subtype (CT/GA)F82.5 vs 50%, Po0.05. These results suggest a major role for GpIa/IIa polymorphisms in the pathogenesis of RVO.

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Relation Between Folate Status, a Common Mutation in Methylenetetrahydrofolate Reductase, and Plasma Homocysteine Concentrations

Cited by 1,297 publications

References 8 publications

Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype. Inter99 (7)

Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype. Inter99 (7)

Evidence for sex differences in the determinants of homocysteine concentrations

The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion

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