title: The C677T MTHFR genotypes influence the efficacy of B9 and B12 vitamins supplementation to lowering plasma total homocysteine in hemodialysis.
abstract: BACKGROUND
  Hyperhomocysteinaemia, an independent risk factor for cardiovascular diseases, is common in hemodialysis patients (HD) and particularly in those homozygous for polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. B vitamins supplementation has been shown to lower plasma total homocysteine (tHcy), but this has been contreversed in several groups. The aim of our study was to explore the response of tHcy in hemodialysis (HD) patients to individual supplementation with folic acid (B9) and/or vitamin B12, based on carrier status for the (MTHFR) polymorphism.
  
  
  METHODS
  132HD were randomized according to C677TMTHFR genotypes into 2 groups (AandB). The group (A) was treated initially with B9 (10mg/day orally) for 2 months (t1) and then with B12 vitamin (cyanocobalamin ampoule of 1000 μg) for the following 2 months (t2), then association of B9 and B12 for 2 months (t3). The group (B) was supplemented initially with vitamin B12 (t1), then with folic acid (t2) and then B9 + B12 for 2 months (t3). A wash-out period of 2 months followed the treatment in both groups (t4). We determined tHcy, B9 and B12 concentrations at each time.
  
  
  RESULTS
  In group A, we noted that the decrease in tHcy becomes significant for CC when patients were supplemented with vit B12 only (p = 0.009). While, B9 + vit B12 supplementation did not seem to improve a significant effect compared with B12 alone. For genotypes (CT) and (TT) we noticed a significant decrease in tHcy at t1 (p = 0.038; 0.005 respectively) and at (t3; CT p = 0.024; TT p = 0.017). In group B, for genotypes CC, the decrease in tHcy became significant at t3 (vit B12 + B9; p = 0.031). For genotypes (CT) and (TT), at the replacement of vit B12 by B9, tHcy was significantly decreased (p = 0.036; 0.012, respectively). The combination of the 2 vitamins (t3) showed no difference compared to folate alone. In the 2 groups (t4), there was an significant increase of tHcy again for 3 genotypes.
  
  
  CONCLUSIONS
  Supplementation with B vitamins correlated to the MTHFR genotypes has been shown to lower significantly tHcy in HD patients.
authors.affiliation: Biochemistry Department, Lr 12 Sp11, Sahloul University Hospital, Sousse, 4054, Tunisia. achour_ons@hotmail.com.
authors.forename: Ons
authors.initials: O
authors.lastname: Achour
authors.affiliation: Nephrology Department, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Sahbi
authors.initials: S
authors.lastname: Elmtaoua
authors.affiliation: Nephrology Department, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Dorsaf
authors.initials: D
authors.lastname: Zellama
authors.affiliation: Biochemistry Department, Lr 12 Sp11, Sahloul University Hospital, Sousse, 4054, Tunisia.
authors.forename: Asma
authors.initials: A
authors.lastname: Omezzine
authors.affiliation: Biochemistry Department, Lr 12 Sp11, Sahloul University Hospital, Sousse, 4054, Tunisia.
authors.forename: Amira
authors.initials: A
authors.lastname: Moussa
authors.affiliation: Biochemistry Department, Lr 12 Sp11, Sahloul University Hospital, Sousse, 4054, Tunisia.
authors.forename: Jihene
authors.initials: J
authors.lastname: Rejeb
authors.affiliation: Biochemistry Department, Lr 12 Sp11, Sahloul University Hospital, Sousse, 4054, Tunisia.
authors.forename: Imene
authors.initials: I
authors.lastname: Boumaiza
authors.affiliation: Biochemistry Department, Lr 12 Sp11, Sahloul University Hospital, Sousse, 4054, Tunisia.
authors.forename: Lobna
authors.initials: L
authors.lastname: Bouacida
authors.affiliation: Biochemistry Department, Lr 12 Sp11, Sahloul University Hospital, Sousse, 4054, Tunisia.
authors.forename: Nabila Ben
authors.initials: NB
authors.lastname: Rejeb
authors.affiliation: Nephrology Department, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Achour
authors.affiliation: Biochemistry Department, Lr 12 Sp11, Sahloul University Hospital, Sousse, 4054, Tunisia.
authors.forename: Ali
authors.initials: A
authors.lastname: Bouslama
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D019587:Dietary Supplements; D015536:Down-Regulation; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D006435:Renal Dialysis / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome; D014416:Tunisia; D014805:Vitamin B 12 / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D014815:Vitamins; D006710:Homocysteine; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12
keywords: (tHCy); B9 and B12 vitamins; Hemodialysis patients (HD); MTHFR genotypes; plasma total Homocysteine