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Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients.
Am J Kidney Dis 2002; 39(5):1032-9AJ

Abstract

Hyperhomocysteinemia, a well-recognized cardiovascular risk factor, is frequent in hemodialysis (HD) patients. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C-->T substitution at nucleotide 677, is associated with homocysteine (Hcy) level elevation. We examined whether three factors involved in the methionine cycle could influence plasma Hcy concentrations in HD patients: MTHFR polymorphism; vitamin B12, an essential cofactor; and folate, the substrate. In a cross-sectional study, serum vitamin B12, folate, and plasma Hcy were measured and MTHFR genotyping was performed in 534 HD patients. Effects of MTHFR genotypes, vitamin B12, and folate on plasma Hcy levels were examined in 450 HD patients not administered vitamin B12 or folate. To examine the effect of vitamin B12 on plasma Hcy concentrations, we compared plasma Hcy concentrations in HD patients with and without vitamin B12 supplementation. To examine whether functional vitamin B12 deficiency exists even in HD patients with normal vitamin B12 concentrations, 15 HD patients (serum vitamin B12 concentrations, 250 to 2,100 pg/mL) were treated with vitamin B12 (mecobalamin, 1.5 mg/d) for 8 weeks. Serum concentrations of methylmalonic acid (MMA) and vitamin B12 were measured. Hcy levels were higher and folate levels were lower in patients with the TT and CT genotypes compared with patients with the CC genotype. Analysis of covariance to determine independent predictors of high Hcy levels identified low serum vitamin B12 and folate levels and high albumin (Alb) levels in CC-genotype patients, low folate levels and high Alb levels in CT-genotype patients, and low folate levels in TT-genotype patients. Plasma Hcy levels were lower in CC- and CT-genotype patients with vitamin B12 supplementation than in those without supplementation. Vitamin B12 supplementation for 8 weeks significantly reduced MMA concentrations in HD patients with normal serum vitamin B12 concentrations. These results indicate that MTHFR genotype influences the correlation of Hcy level with vitamin B12 and folate levels in HD patients. Functional vitamin B12 deficiency may exist, even in HD patients with normal vitamin B12 concentrations. The efficacy of vitamin B12 and folate supplementation on plasma Hcy levels may depend on MTHFR genotype.

Authors+Show Affiliations

Division of Blood Transfusion and Mathematical Informative Science, Yamanashi Medical University, Tago Clinic, Yamanashi, Japan. highway@athena.ocn.ne.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11979347

Citation

Nakamura, Takamichi, et al. "Methylenetetrahydrofolate Reductase Genotype, Vitamin B12, and Folate Influence Plasma Homocysteine in Hemodialysis Patients." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 39, no. 5, 2002, pp. 1032-9.
Nakamura T, Saionji K, Hiejima Y, et al. Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients. Am J Kidney Dis. 2002;39(5):1032-9.
Nakamura, T., Saionji, K., Hiejima, Y., Hirayama, H., Tago, K., Takano, H., ... Hata, A. (2002). Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 39(5), pp. 1032-9.
Nakamura T, et al. Methylenetetrahydrofolate Reductase Genotype, Vitamin B12, and Folate Influence Plasma Homocysteine in Hemodialysis Patients. Am J Kidney Dis. 2002;39(5):1032-9. PubMed PMID: 11979347.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients. AU - Nakamura,Takamichi, AU - Saionji,Katsu, AU - Hiejima,Yoshimitsu, AU - Hirayama,Hideo, AU - Tago,Kiichiro, AU - Takano,Hajime, AU - Tajiri,Munemasa, AU - Hayashi,Katsuji, AU - Kawabata,Masaki, AU - Funamizu,Makiko, AU - Makita,Yoshio, AU - Hata,Akira, PY - 2002/4/30/pubmed PY - 2002/6/21/medline PY - 2002/4/30/entrez SP - 1032 EP - 9 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am. J. Kidney Dis. VL - 39 IS - 5 N2 - Hyperhomocysteinemia, a well-recognized cardiovascular risk factor, is frequent in hemodialysis (HD) patients. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C-->T substitution at nucleotide 677, is associated with homocysteine (Hcy) level elevation. We examined whether three factors involved in the methionine cycle could influence plasma Hcy concentrations in HD patients: MTHFR polymorphism; vitamin B12, an essential cofactor; and folate, the substrate. In a cross-sectional study, serum vitamin B12, folate, and plasma Hcy were measured and MTHFR genotyping was performed in 534 HD patients. Effects of MTHFR genotypes, vitamin B12, and folate on plasma Hcy levels were examined in 450 HD patients not administered vitamin B12 or folate. To examine the effect of vitamin B12 on plasma Hcy concentrations, we compared plasma Hcy concentrations in HD patients with and without vitamin B12 supplementation. To examine whether functional vitamin B12 deficiency exists even in HD patients with normal vitamin B12 concentrations, 15 HD patients (serum vitamin B12 concentrations, 250 to 2,100 pg/mL) were treated with vitamin B12 (mecobalamin, 1.5 mg/d) for 8 weeks. Serum concentrations of methylmalonic acid (MMA) and vitamin B12 were measured. Hcy levels were higher and folate levels were lower in patients with the TT and CT genotypes compared with patients with the CC genotype. Analysis of covariance to determine independent predictors of high Hcy levels identified low serum vitamin B12 and folate levels and high albumin (Alb) levels in CC-genotype patients, low folate levels and high Alb levels in CT-genotype patients, and low folate levels in TT-genotype patients. Plasma Hcy levels were lower in CC- and CT-genotype patients with vitamin B12 supplementation than in those without supplementation. Vitamin B12 supplementation for 8 weeks significantly reduced MMA concentrations in HD patients with normal serum vitamin B12 concentrations. These results indicate that MTHFR genotype influences the correlation of Hcy level with vitamin B12 and folate levels in HD patients. Functional vitamin B12 deficiency may exist, even in HD patients with normal vitamin B12 concentrations. The efficacy of vitamin B12 and folate supplementation on plasma Hcy levels may depend on MTHFR genotype. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/11979347/Methylenetetrahydrofolate_reductase_genotype_vitamin_B12_and_folate_influence_plasma_homocysteine_in_hemodialysis_patients_ DB - PRIME DP - Unbound Medicine ER -