Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients

Nakamura, Takamichi; Saionji, Katsu; Hiejima, Yoshimitsu; Hirayama, Hideo; Tago, Kiichiro; Takano, Hajime; Tajiri, Munemasa; Hayashi, Kanako; Kawabata, Masaki; Funamizu, Makiko; Makita, Yoshio; Hata, Akira

doi:10.1053/ajkd.2002.32779

Cited by 10 publications

(5 citation statements)

References 34 publications

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“…Group B vitamins regulate the homocysteine metabolism and the efficacy of B vitamins administration on plasma tHcy level was described to depend on MTHFR genotype. 38 Although a great number of our patients with TT genotype were deficient in folic acid, we did not find a clear association between the vitamin status and level of this amino acid. This suggests that the sole substitution with vitamin B could not be sufficient to correct tHcy levels in an ESRD population.…”

Section: Discussioncontrasting

confidence: 62%

Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort

Pernod

Bosson

Golshayan³

et al. 2006

Kidney International

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Cardiovascular disease (CVD) remains the major cause of death in patients with end-stage renal disease (ESRD). Traditional risk factors do not explain the high prevalence of CVD in this population, and other non-traditional cardiovascular (CV) risk markers have now been described. Therefore, the potential relationship between CVD and phenotypic and genotypic risk markers was investigated prospectively in incident dialysis patients cohort. The 279 patients (244 on hemodialysis, 35 on peritoneal dialysis) within the Diamant Alpin Dialysis Cohort Study were investigated. Phenotypic and genotypic parameters were determined at dialysis initiation, patients monitored over a 2-year period, and CV events (morbidity and mortality) recorded. Globally, 82 CV events occurred and 26 patients (9.3%) died from CVD, whereas 28 (10%) died from non-CV causes. Previous CV events were strongly predictive of CV events occurrence, whatever patients had had one (hazard ratio (HR) 2, 95% confidence intervals (CI) 1.1-3.5) or more (HR 3.9, 95% CI 2.1-7.1) CV accidents before starting dialysis. Both lipoprotein(a) (HR 1.67, 95% CI 1-2.5) and total plasma homocysteine at cutoff 30 micromol/l (HR 1.7, 95% CI 1.1-2.8) were independent predictors of CV events outcome. In the subgroup of patients with homocysteine < 30 micromol/l, methylenetetrahydrofolate reductase (MTHFR) TT was the sole biological parameter predictive of CV event outcome (HR 2.5, 95% CI 1.1-10, P = 0.03). ESRD patients who enter chronic dialysis with a previous CV event, high total homocysteinemia levels, or MTHFR 677TT genotype must be considered at high risk of incident CV events.

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Section: Discussioncontrasting

confidence: 62%

Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort

Pernod

Bosson

Golshayan³

et al. 2006

Kidney International

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“…A previous study demonstrated that a mutation of MTHFR C677T increases sHcy concentration and decreases folate [38]. Hemodialysis patients with the TT and CT genotypes of the MTHFR gene have significantly greater sHcy and lower serum folate concentrations than those with the CC genotype [39]. The TT genotype had clearly higher levels of homocysteine than CT heterozygotes or CC homozygotes [40].…”

Section: Discussionmentioning

confidence: 95%

The Different Relationship between Homocysteine and Uric Acid Levels with Respect to the MTHFR C677T Polymorphism According to Gender in Patients with Cognitive Impairment

et al. 2020

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In an elderly population with cognitive impairment, we investigated the association between serum uric acid (sUA) and serum homocysteine (sHcy), known risk factors for cerebrovascular disease. We also investigated the potential effect of the C677T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) to the sUA level in different dementia types. Participants underwent a battery of tests including measurements of sUA, sHcy, folic acid, and vitamin B12 as well as genotyping of the MTHFR locus. Data from 861 subjects (597 females to 264 males) were retrospectively analyzed. Subjects with hyperhomocysteinemia had lower serum folic acid and vitamin B12 and higher sUA than those with normal sHcy. sUA was significantly associated with serum creatinine, HbA1c, and sHcy regardless of gender. The TT genotype was found to be associated with hyperhomocysteinemia in both genders (p = 0.001). The levels of hyperlipidemia, sHcy, and sUA differed according to dementia subtypes. High sUA were associated with hyperhomocystenemia in TT genotype only in dementia with vascular lesion. This study reveals that sUA is positively associated with sHcy. We speculate that the two markers synergistically increase cerebrovascular burden and suggested that dietary intervention for sUA and sHcy would be helpful for cognitive decline with vascular lesion.

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“…Guttormsen et al (1996) made an observation that all hyperhomocysteinemic subjects with the C/C genotype had low plasma vitamin B 12 concentrations, and that vitamin B 12 supplementation alone had reduced their plasma homocysteine concentrations. Nakamura et al (2002) explained the reason for the above observation as follows: subjects with the C/T or T/T genotype have lower folate concentrations than those with the C/C genotype because of a reduced production of 5-methyl THF, a product of MTHFR. Low 5-methyl THF concentrations in the cytosol might conceal a deficiency of vitamin B 12 in patients with the C/T or T/T.…”

Section: Discussionmentioning

confidence: 99%

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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Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients

Cited by 10 publications

References 34 publications

Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort

Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort

The Different Relationship between Homocysteine and Uric Acid Levels with Respect to the MTHFR C677T Polymorphism According to Gender in Patients with Cognitive Impairment

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

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