title: Effect of folic acid intervention on the change of serum folate level in hypertensive Chinese adults:  do methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms affect therapeutic responses?
abstract: OBJECTIVE
  To assess the influence of individual methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase A2756G polymorphisms on the change of serum folate concentration in response to different dosages and durations of folic acid (FA) supplementation in hypertensive Chinese adults.
  
  
  METHODS
  A total of 480 patients with mild or moderate essential hypertension were randomly assigned to three treatment groups: (a) enalapril only (10 mg, control group); (b) enalapril FA tablet [10 : 0.4 mg (10 mg of enalapril combined with 0.4 mg of FA), low-FA group]; (c) enalapril FA tablet (10 : 0.8 mg, high-FA group), once daily for 8 weeks. Individual serum folate levels were measured at baseline, and at 4 and 8 weeks posttreatment.
  
  
  RESULTS
  After 4 or 8 weeks of treatment, increases in serum folate were seen across all genotypes and FA dosage groups. However, compared with patients with 677CC genotype, those with CT or TT genotype in the low-FA group and TT genotype in the high-FA group still had significantly lower folate concentrations, particularly women. In the low-FA group, patients with CT or TT genotype showed an attenuated response compared with those with CC genotype (median ratio of folate at week 8 to that at baseline: CC,1.953 vs. CT,1.755 or TT,1.637, P<0.01 for both). Such an attenuated response was not observed in the high-FA group. Yet, only in the high-FA group did serum folate appear to reach a plateau after 4 weeks of treatment in all three MTHFR 677 genotypes and the methionine synthase 2756 AG/GG genotype.
  
  
  CONCLUSIONS
  We demonstrated that MTHFR C677T polymorphisms can not only affect serum folate levels at the baseline and post-FA treatment, but also therapeutic responses to various dosages and durations of FA supplementation.
authors.affiliation: Institute of Biomedicine, Anhui Medical University, Hefei, P.R. China.
authors.forename: Xianhui
authors.initials: X
authors.lastname: Qin
authors.forename: Jianping
authors.initials: J
authors.lastname: Li
authors.forename: Yimin
authors.initials: Y
authors.lastname: Cui
authors.forename: Zeyuan
authors.initials: Z
authors.lastname: Liu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
authors.forename: Deming
authors.initials: D
authors.lastname: Guan
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.forename: Yanni
authors.initials: Y
authors.lastname: Wang
authors.forename: Fumin
authors.initials: F
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
authors.forename: Xiping
authors.initials: X
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: Huo
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics*; D002681:China; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase