Common Methylenetetrahydrofolate Reductase Gene Mutation Leads to Hyperhomocysteinemia but Not to Vascular Disease

Brattström, Lars; Wilcken, D. E. L.; Öhrvik, John; Brudin, Lars

doi:10.1161/01.cir.98.23.2520

Cited by 595 publications

(390 citation statements)

References 46 publications

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“…In our study, serum homocysteine concentrations were found significantly higher in pregnant women with the T/T genotype, as compared to those in the C/T or C/C genotype, confirming the results of other investigators (Jacques et al, 1996;Brattstrom et al, 1998;Gudnason et al, 1998). Serum homocysteine was negatively correlated with serum folate in our study subjects of all the three MTHFR genotypes, and the correlation between the two serum levels was strongest as had been previously reported by Ueland et al (2001) and Guttormsen et al (1996), who had observed a steeper negative slope in plots of serum folate vs serum homocysteine concentration in T/T individuals compared to those in the C/T or C/C subjects.…”

Section: Discussionsupporting

confidence: 92%

“…In our study, pregnant women who were homozygotes for the MTHFR mutation had higher fasting homocysteine levels only when their serum folate levels were below the median, but not when serum folate levels were above the median. This confirms the study of Brattstrom et al (1998) and Bailey and Gregory III (1999), who reported that the association between the MTHFR genotype and homocysteine levels was modified by serum folate status. One explanation for these observations could be, as hypothesized by Jacques et al (1996), that a higher folate status may increase the in vivo stability of the MTHFR enzyme, thus reducing the difference in enzyme activity between the T/T and C/T or C/C genotype.…”

Section: Discussionsupporting

confidence: 91%

“…The homozygosity for the C677T variant MTHFR allele causes higher fasting plasma homocysteine concentrations and lower folate status than heterozygous or wild-type groups (Brattstrom et al, 1998). A curve of steeper slope in subjects with T/T than in those of C/C genotype has been reported for an inverse relation between plasma homocysteine and folate (van der Put et al, 1995;Nelen et al, 1998) or vitamin B 12 (Jacques et al, 1996;Woodside et al, 1998;Moriyama et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

Kim

Chang

2003

Eur J Clin Nutr

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Objective: The purpose of this study was to investigate the effect of the interaction between the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes and serum levels of B vitamins on serum homocysteine levels in pregnant women. Design: A cross-sectional study. Setting: Ewha Womans University Hospital, Seoul, Korea. Subjects: A total of 177 normal pregnant women, 24.671.1 weeks of gestation, in a 6-month period during [2001][2002]. Interventions: Serum vitamin B 2 , vitamin B 6 , and homocysteine analyses were conducted using high-performance liquid chromatography methods. Serum folate and vitamin B 12 concentrations were determined using a radioimmunoassay kit. MTHFR gene mutation was investigated by the polymerase chain reaction of a genomic DNA fragment. Results: Serum homocysteine was higher in women with the T/T genotype than those with the C/T or C/C genotype of the MTHFR gene (Po0.05). Serum homocysteine was negatively correlated with serum folate in all MTHFR genotypes (Po0.001), and the correlation between the two serum levels was the strongest in the T/T genotype. Serum homocysteine was higher in the subjects with the T/T MTHFR genotype only when the serum folate was below the median level. Explanatory power of B vitamin status as predictors of serum homocysteine levels was more pronounced in the T/T genotypes (68.5%) compared with the C/T (37.9%) or C/C genotypes (20.6%). Conclusions: Serum homocysteine levels in pregnant women varied significantly with MTHFR genotype and the serum B vitamin status. Higher serum folate, vitamin B 2 , and vitamin B 12 concentrations may lessen the MTHFR genotypic effect on serum homocysteine levels.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

Kim

Chang

2003

Eur J Clin Nutr

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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%

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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“…16 The reported prevalence of the homozygous 677C4T (TT) genotype is between 0 and 32% of the population world-wide, 17 ranging from 5 to 15% in Caucasian populations. 18 The single amino-acid substitution results in impaired flavin adenine dinucleotide (FAD) binding, leading to loss of folate resulting, in its turn, in reduced activity of MTHFR. 19 Subjects with the TT genotype have about 25% higher homocysteine levels than those with the normal homozygous (CC) genotype, 18 whereby the impact of the polymorphism varies according to folate or riboflavin status.…”

Section: Introductionmentioning

confidence: 99%

Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis

Muntjewerff¹,

et al. 2005

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Elevated plasma homocysteine concentration has been suggested as a risk factor for schizophrenia, but the results of epidemiological studies have been inconsistent. The most extensively studied genetic variant in the homocysteine metabolism is the 677C4T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, resulting in reduced enzyme activity and, subsequently, in elevated homocysteine. A meta-analysis of eight retrospective studies (812 cases and 2113 control subjects) was carried out to examine the association between homocysteine and schizophrenia. In addition, a meta-analysis of 10 studies (2265 cases and 2721 control subjects) on the homozygous (TT) genotype of the MTHFR 677C4T polymorphism was carried out to assess if this association is causal. A 5 lmol/l higher homocysteine level was associated with a 70% (95% confidence interval, CI: 27-129) higher risk of schizophrenia. The TT genotype was associated with a 36% (95% CI: 7-72) higher risk of schizophrenia compared to the CC genotype. The performed meta-analyses showed no evidence of publication bias or excessive influence attributable to any given study. In conclusion, our study provides evidence for an association of homocysteine with schizophrenia. The elevated risk of schizophrenia associated with the homozygous genotype of the MTHFR 677C4T polymorphism provides support for causality between a disturbed homocysteine metabolism and risk of schizophrenia.

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Common Methylenetetrahydrofolate Reductase Gene Mutation Leads to Hyperhomocysteinemia but Not to Vascular Disease

Cited by 595 publications

References 46 publications

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

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

Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis

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