PMID- 31864233
OWN - NLM
STAT- MEDLINE
DCOM- 20210715
LR  - 20210715
IS  - 1521-2254 (Electronic)
IS  - 1099-498X (Linking)
VI  - 22
IP  - 4
DP  - 2020 Apr
TI  - CBS gene polymorphism and promoter methylation-mediating effects on the efficacy 
      of folate therapy in patients with hyperhomocysteinemia.
PG  - e3156
LID - 10.1002/jgm.3156 [doi]
AB  - BACKGROUND: A decrease in cystathionine beta-synthase (CBS) enzyme activity could 
      lead to hyperhomocysteinemia (HHcy). Studies have revealed that DNA methylation 
      has a mediating effect on the development of diseases. The present study aimed to 
      explore CBS promoter methylation-mediating effects on the efficacy of folate 
      treatment for HHcy. METHODS: HHcy patients were treated with folate (5 mg/day) 
      for 90 days and then divided into a failure group (Hcy >/= 15 mumol/l) and a success 
      group (Hcy < 15 mumol/l) according to post-treatment plasma Hcy levels. Genotyping 
      of CBS gene (rs2851391 and rs706209) in patients (n = 638) was detected using a 
      MassArray system (Sequenom, San Diego, CA, USA). The baseline DNA methylation 
      levels of patients (n = 299) were detected using MethylTarget technology 
      (Genesky Biotechnologies Inc., Shanghai, China). RESULTS: The CBS rs2851391 TC + 
      CC genotype was related to a 57% reduction of failure risk in HHcy treatment 
      compared to the TT genotype (95% confidence interval [CI] = 0.19-0.97). The CBS 
      rs706209 CT + TT genotype had a 2.97-fold increased risk of failure to treatment 
      compared to the CC genotype (95% CI = 1.52-5.80). After adjustment for 
      confounding factors, the odds ratio (95% CI) for the risk of failure in HHcy 
      treatment in total and male patients was 0.55 (0.32-0.93) and 0.34 (0.16-0.69), 
      respectively, for patients with higher methylation levels (>/= methylation median). 
      Additionally, baseline CBS promoter methylation mediated 33.39% of the effect of 
      rs2851391 on the efficacy of folate treatment for HHcy (ACME [average causal 
      mediation effects]: -0.05, 95% CI = -0.11 to 0.00, p = 0.046). CONCLUSIONS: The 
      present study indicates that CBS gene polymorphism and promoter methylation could 
      affect the efficacy of HHcy. There were potentially causal effects of genetic, 
      epigenetic variations at the CBS rs2851391 locus on the efficacy of HHcy therapy 
      with folate.
CI  - (c) 2019 John Wiley & Sons, Ltd.
FAU - Zhao, Qinglin
AU  - Zhao Q
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, Henan, People's Republic of China.
FAU - Zhang, Chengda
AU  - Zhang C
AD  - Department of International Medicine, Beaumont Health System, Royal Oak, MI, USA.
FAU - Li, Dankang
AU  - Li D
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, Henan, People's Republic of China.
FAU - Huang, Xiaowen
AU  - Huang X
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, Henan, People's Republic of China.
FAU - Ren, Bingnan
AU  - Ren B
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, Henan, People's Republic of China.
FAU - Yue, Limin
AU  - Yue L
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, Henan, People's Republic of China.
FAU - Du, Binghui
AU  - Du B
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, Henan, People's Republic of China.
FAU - Godfrey, Opolot
AU  - Godfrey O
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, Henan, People's Republic of China.
FAU - Zhang, Weidong
AU  - Zhang W
AUID- ORCID: 0000-0002-0314-7820
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, Henan, People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200119
PL  - England
TA  - J Gene Med
JT  - The journal of gene medicine
JID - 9815764
RN  - 0 (Biomarkers)
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Biomarkers
MH  - Cystathionine beta-Synthase/*genetics
MH  - *DNA Methylation
MH  - Female
MH  - Folic Acid/administration & dosage/*therapeutic use
MH  - Gene Frequency
MH  - Genotype
MH  - Humans
MH  - Hyperhomocysteinemia/*drug therapy/*genetics
MH  - Male
MH  - Middle Aged
MH  - Odds Ratio
MH  - Pharmacogenetics/methods
MH  - Pharmacogenomic Variants
MH  - *Polymorphism, Genetic
MH  - Polymorphism, Single Nucleotide
MH  - *Promoter Regions, Genetic
MH  - Treatment Outcome
OTO - NOTNLM
OT  - CBS
OT  - hyperhomocysteinemia
OT  - mediating effect
OT  - polymorphism
OT  - promoter methylation
EDAT- 2019/12/22 06:00
MHDA- 2021/07/16 06:00
CRDT- 2019/12/22 06:00
PHST- 2019/05/07 00:00 [received]
PHST- 2019/12/01 00:00 [revised]
PHST- 2019/12/18 00:00 [accepted]
PHST- 2019/12/22 06:00 [pubmed]
PHST- 2021/07/16 06:00 [medline]
PHST- 2019/12/22 06:00 [entrez]
AID - 10.1002/jgm.3156 [doi]
PST - ppublish
SO  - J Gene Med. 2020 Apr;22(4):e3156. doi: 10.1002/jgm.3156. Epub 2020 Jan 19.