PMID- 32404901
OWN - NLM
STAT- MEDLINE
DCOM- 20210624
LR  - 20210624
IS  - 1476-5640 (Electronic)
IS  - 0954-3007 (Linking)
VI  - 74
IP  - 12
DP  - 2020 Dec
TI  - Association between gene promoter methylation of the one-carbon metabolism 
      pathway and serum folate among patients with hyperhomocysteinemia.
PG  - 1677-1684
LID - 10.1038/s41430-020-0657-9 [doi]
AB  - AIM: Age and lower folate concentrations are well-known risk factors for 
      cardiovascular disease (CVD), but the potential roles of age and folate 
      deficiency in hyperhomocysteinemia (HHcy), especially in HHcy patients with 
      abnormal methylation levels of key enzyme genes promoter in homocysteinemia (Hcy) 
      pathway, have not been thoroughly evaluated. The purpose of this study was to 
      evaluate the relationship between the promoter methylation levels of six key 
      enzyme genes and age and serum folate level to better understand the pathogenesis 
      of HHcy. METHODS: In 299 HHcy patients, six key enzyme genes promoter methylation 
      was analyzed by PCR amplification and MethylTarget(TM) methods. RESULTS: The 
      betaine homocysteine methyltransferase (BHMT), Cystathionine beta-synthase (CBS), 
      and Methionine synthasegene (MTR) promoter methylation levels were positively 
      associated with age and a negative correlation was found between CBS promoter 
      methylation level and folate levels. However, these associations were not 
      significant after Bonferroni correction. The stratified analysis showed that the 
      methylation level of CBS gene promoter was positively correlated with age in 
      males, and a positive correlation was also found between BHMT gene promoter 
      methylation level and age in HHcy patients with a history of diabetes or 
      hypertension. Moreover, stratified analysis according to sex revealed that the 
      methylation levels of three CpG regions of BHMT_2, CBS_2, and CBS_3 were 
      positively correlated with age in males after Bonferroni correction. CONCLUSIONS: 
      Our data suggested that age and folate deficiency may increase the risk of HHcy 
      by mediating methylation of the promoter regions of key enzyme genes in the 
      one-carbon metabolism pathway.
FAU - Huang, Xiaowen
AU  - Huang X
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 - Li, Dankang
AU  - Li D
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, 450001, Henan, China.
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 - Shi, Fengxian
AU  - Shi F
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 - Zheng, Caifang
AU  - Zheng C
AD  - Department of Epidemiology, School of Public Health, Zhengzhou University, 
      Zhengzhou, 450001, Henan, China.
FAU - Chen, Xiaorui
AU  - Chen X
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 - 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 - 20200513
PL  - England
TA  - Eur J Clin Nutr
JT  - European journal of clinical nutrition
JID - 8804070
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 7440-44-0 (Carbon)
RN  - 935E97BOY8 (Folic Acid)
SB  - IM
MH  - Carbon
MH  - Folic Acid
MH  - Homocysteine
MH  - Humans
MH  - *Hyperhomocysteinemia/genetics
MH  - Male
MH  - Methylation
MH  - Promoter Regions, Genetic
EDAT- 2020/05/15 06:00
MHDA- 2021/06/25 06:00
CRDT- 2020/05/15 06:00
PHST- 2019/12/03 00:00 [received]
PHST- 2020/04/30 00:00 [accepted]
PHST- 2020/04/29 00:00 [revised]
PHST- 2020/05/15 06:00 [pubmed]
PHST- 2021/06/25 06:00 [medline]
PHST- 2020/05/15 06:00 [entrez]
AID - 10.1038/s41430-020-0657-9 [pii]
AID - 10.1038/s41430-020-0657-9 [doi]
PST - ppublish
SO  - Eur J Clin Nutr. 2020 Dec;74(12):1677-1684. doi: 10.1038/s41430-020-0657-9. Epub 
      2020 May 13.