PMID- 32203239
OWN - NLM
STAT- MEDLINE
DCOM- 20210624
LR  - 20210624
IS  - 1476-5640 (Electronic)
IS  - 0954-3007 (Linking)
VI  - 74
IP  - 7
DP  - 2020 Jul
TI  - Association of genetic and epigenetic variants in one-carbon metabolism gene with 
      folate treatment response in hyperhomocysteinaemia.
PG  - 1073-1083
LID - 10.1038/s41430-020-0611-x [doi]
AB  - BACKGROUND: Folate supplementation treatment is the first-line therapy in 
      hyperhomocysteinaemia (HHcy). Up to 40% of HHcy patients do not benefit from 
      folate therapy. Genetic and epigenetic factors of one-carbon metabolism (1-CM) 
      might be identified as a predictor of folate supplementation treatment response. 
      In the present study, we attempt to identify whether genetic and epigenetic 
      factors might predict folate treatment response. METHODS: A total of 230 patients 
      with HHcy were involved in this prospective cohort study. Differences between 
      baseline concentrations and concentrations obtained at 90 days of treatment were 
      calculated to evaluate the treatment response. General linear models and Pearson 
      correlation was used to explore associations among single-nucleotide 
      polymorphisms (SNPs), DNA methylation, and folate treatment response. Finally, 
      mediation analysis was performed to investigate whether DNA methylation of MTRR 
      mediates the association between SNPs and treatment response. RESULTS: MTHFD 
      rs1950902 and MTRR rs162036, rs1801394 was associated with the folate treatment 
      response (P = 0.000, 0.048, and 0.043, respectively). CBS and CBS_2 DNA 
      methylation was significantly associated with folate treatment response 
      (P = 0.0009 and < 0.001). DNA methylation of MTHFR, MTR, and MTRR was also 
      significantly associated with folate treatment response (P < 0.001). DNA 
      methylation of MTRR and MTRR_1 mediated 40.71% and 40.47% of the effect of 
      rs1801394 on folate treatment response, respectively. CONCLUSIONS: Our results 
      indicated that the 1-CM gene SNPs and DNA methylation was associated with folate 
      treatment response and can be further evaluated relationship between SNPs and DNA 
      methylation in 1-CM with treatment response in a larger sample.
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 - Huang, Xiaowen
AU  - Huang X
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, 450001, Henan, China.
FAU - Zhang, Chengda
AU  - Zhang C
AD  - Department of International Medicine, Beaumont Health System, Royal Oak, MI, 
      48073, USA.
FAU - Godfrey, Opolot
AU  - Godfrey O
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
PT  - Research Support, Non-U.S. Gov't
DEP - 20200320
PL  - England
TA  - Eur J Clin Nutr
JT  - European journal of clinical nutrition
JID - 8804070
RN  - 7440-44-0 (Carbon)
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
SB  - IM
MH  - Carbon
MH  - Epigenesis, Genetic
MH  - *Folic Acid
MH  - Genotype
MH  - Humans
MH  - *Methylenetetrahydrofolate Reductase (NADPH2)/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Prospective Studies
EDAT- 2020/03/24 06:00
MHDA- 2021/06/25 06:00
CRDT- 2020/03/24 06:00
PHST- 2019/10/15 00:00 [received]
PHST- 2020/03/10 00:00 [accepted]
PHST- 2020/03/05 00:00 [revised]
PHST- 2020/03/24 06:00 [pubmed]
PHST- 2021/06/25 06:00 [medline]
PHST- 2020/03/24 06:00 [entrez]
AID - 10.1038/s41430-020-0611-x [pii]
AID - 10.1038/s41430-020-0611-x [doi]
PST - ppublish
SO  - Eur J Clin Nutr. 2020 Jul;74(7):1073-1083. doi: 10.1038/s41430-020-0611-x. Epub 
      2020 Mar 20.