title: The C677T thermolabile variant of methylene tetrahydrofolate reductase on homocysteine, folate and vitamin B12 in a hemodialysis center.
abstract: Homocysteine is a risk factor for cardiovascular disease. Mutations in a key enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase, may contribute to hyperhomocysteinemia and alter folate and cobalamin levels. After starting hemodialysis, 10 mg oral folate daily and 500 micrograms intravenous methylcobalamin once weekly were prescribed to 27 hemodialysis patients (time on hemodialysis > or = 12 months) and two groups were defined: Group A normal; Group B heterozygous. Initial, third and twelfth month measurements of homocysteine, serum folate and vitamin B12 levels were collected and analyzed. Heterozygous state of methylenetetrahydrofolate reductase prevalence was 48% and homozygozity 4%. Hyperhomocysteinemia was present in both groups. Cobalamin final levels were significantly lower in Group B compared to Group A. Homocysteine, serum folate and cobalamin levels at third and twelfth month were significantly different from baseline levels but non-different between them in both groups. In Group B, vitamin B12 at third month was significantly higher than initial, but final measurements were not different from baseline determinations. In conclusion, the heterozygous prevalence of the enzyme in hemodialysis patients is similar to that reported in the general population; hyperhomocysteinemia is frequent in hemodialysis patients and final levels in heterozygous patients are significantly higher than in normal patients. Cobalamin levels are lower in the heterozygous group. After one year of treatment, homocysteine tends to increase, suggesting a secondary resistance phenomenon to vitamin supplementation in heterozygous patients.
authors.affiliation: Servicio de Nefrología, Nuclear Hospital Británico, Perdriel 74, 1280 Buenos Aires, Argentina. htrimarchi@hotmail.com
authors.forename: Hernán
authors.initials: H
authors.lastname: Trimarchi
authors.forename: Valeria
authors.initials: V
authors.lastname: Genoud
authors.forename: Amalia
authors.initials: A
authors.lastname: Schiel
authors.forename: Maria
authors.initials: M
authors.lastname: Castañon
authors.forename: Emilio
authors.initials: E
authors.lastname: Freixas
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Diaz
authors.forename: Juan
authors.initials: J
authors.lastname: Schropp
authors.forename: Diana
authors.initials: D
authors.lastname: Martino
authors.forename: Horacio
authors.initials: H
authors.lastname: Pereyra
authors.forename: Lucia
authors.initials: L
authors.lastname: Kordich
mesh_terms: D000328:Adult; D016009:Chi-Square Distribution; D005260:Female; D005492:Folic Acid / Q000097:blood* / Q000627:therapeutic use; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood* / Q000235:genetics; D006801:Humans; D020138:Hyperhomocysteinemia / Q000517:prevention & control; D007676:Kidney Failure, Chronic / Q000097:blood / Q000201:enzymology* / Q000628:therapy; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D006435:Renal Dialysis; D018709:Statistics, Nonparametric; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use
chemical_list: D006710:Homocysteine; D005492:Folic Acid; C019476:mecobalamin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12