PMID- 31558761
OWN - NLM
STAT- MEDLINE
DCOM- 20200312
LR  - 20220420
IS  - 1435-232X (Electronic)
IS  - 1434-5161 (Linking)
VI  - 64
IP  - 12
DP  - 2019 Dec
TI  - Association between BHMT and CBS gene promoter methylation with the efficacy of 
      folic acid therapy in patients with hyperhomocysteinemia.
PG  - 1227-1235
LID - 10.1038/s10038-019-0672-7 [doi]
AB  - Both betaine homocysteine methyltransferase (BHMT) and cystathionine beta-synthase 
      (CBS) are major enzymes in the metabolism of plasma homocysteine (Hcy). Abnormal 
      methylation levels of BHMT and CBS are positively associated with Hcy levels. The 
      present study is performed to explore the association between the methylation 
      levels in the promoter regions of the BHMT and CBS genes and the efficacy of 
      folic acid therapy in patient with hyperhomocysteinemia (HHcy). A prospective 
      cohort study recruiting HHcy (Hcy >/= 15 mumol/L) patients was performed. The 
      subjects were treated with oral folic acid (5 mg/d) for 90 days, and the patients 
      were divided into the success group (Hcy < 15 mumol/L) and the failure group 
      (Hcy >/= 15 mumol/L) according to their Hcy levels after treatment. In the logistic 
      regression model with adjusted covariates, the patients with lower total 
      methylation levels in the BHMT and CBS promoter regions exhibited 1.627-fold and 
      1.671-fold increased risk of treatment failure compared with higher methylation 
      individuals, respectively. Similarly, subjects who had lower methylation levels 
      (<methylation mean) in BHMT CpG1 had 1.792 times higher risks. Stratified 
      analysis by sex found that lower CBS methylation levels were associated with a 
      2.128-fold increased risk for treatment failure in males with HHcy. Lower levels 
      of BHMT or CBS promoter total methylation might be associated with increased the 
      risk of treatment failure. These studies suggest that lower levels of BHMT and 
      CBS methylation are all predictors of failure in folic acid therapy for HHcy. 
      However, due to some limitations of this study, such as the small number of the 
      loci tested, further large-scale studies are necessary to verify our 
      observations.
FAU - Huang, Xiaowen
AU  - Huang X
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, 450001, Henan, China.
FAU - Li, Dankang
AU  - Li D
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, 450001, Henan, China.
FAU - Zhao, Qinglin
AU  - Zhao Q
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, 450001, Henan, China.
FAU - Zhang, Chengda
AU  - Zhang C
AD  - Department of Biostatistics and Bioinformatics, School of Public Health and 
      Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
FAU - Ren, Bingnan
AU  - Ren B
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, 450001, Henan, China.
FAU - Yue, Limin
AU  - Yue L
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, 450001, Henan, China.
FAU - Du, Binghui
AU  - Du B
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, 450001, Henan, China.
FAU - Godfrey, Opolot
AU  - Godfrey O
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, 450001, Henan, China.
FAU - Wang, Xiliang
AU  - Wang X
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, 450001, Henan, China.
FAU - Zhang, Weidong
AU  - Zhang W
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, 450001, Henan, China. imooni@163.com.
LA  - eng
PT  - Journal Article
DEP - 20190927
PL  - England
TA  - J Hum Genet
JT  - Journal of human genetics
JID - 9808008
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 2.1.1.5 (BHMT protein, human)
RN  - EC 2.1.1.5 (Betaine-Homocysteine S-Methyltransferase)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Aged
MH  - Betaine-Homocysteine S-Methyltransferase/*genetics
MH  - Cystathionine beta-Synthase/*genetics
MH  - Female
MH  - Folic Acid/*therapeutic use
MH  - Humans
MH  - Hyperhomocysteinemia/*drug therapy/*genetics
MH  - Male
MH  - Methylation
MH  - Middle Aged
MH  - Promoter Regions, Genetic/*genetics
MH  - Prospective Studies
EDAT- 2019/09/29 06:00
MHDA- 2020/03/13 06:00
CRDT- 2019/09/28 06:00
PHST- 2019/06/29 00:00 [received]
PHST- 2019/09/08 00:00 [accepted]
PHST- 2019/09/06 00:00 [revised]
PHST- 2019/09/29 06:00 [pubmed]
PHST- 2020/03/13 06:00 [medline]
PHST- 2019/09/28 06:00 [entrez]
AID - 10.1038/s10038-019-0672-7 [pii]
AID - 10.1038/s10038-019-0672-7 [doi]
PST - ppublish
SO  - J Hum Genet. 2019 Dec;64(12):1227-1235. doi: 10.1038/s10038-019-0672-7. Epub 2019 
      Sep 27.