PMID- 24972087
OWN - NLM
STAT- MEDLINE
DCOM- 20151026
LR  - 20220318
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 6
DP  - 2014
TI  - ABCG1 rs57137919G>a polymorphism is functionally associated with varying gene 
      expression and apoptosis of macrophages.
PG  - e97044
LID - 10.1371/journal.pone.0097044 [doi]
LID - e97044
AB  - ATP-binding cassette transporter G1 (ABCG1) is a transmembrane cholesterol 
      transporter involved in macrophage sterol homeostasis, reverse cholesterol 
      transport (RCT), and atherosclerosis. The role of ABCG1 in atherosclerosis 
      remains controversial, especially in animal models. Our previous study showed 
      that single nucleotide polymorphism rs57137919 (-367G>A) in the ABCG1 promoter 
      region was associated with reduced risk for atherosclerotic coronary artery 
      disease (CAD). This study was designed to provide functional evidence for the 
      role of rs57137919G>A in atherosclerosis in humans. We combined in vitro and ex 
      vivo studies using cell lines and human monocyte-derived macrophages to 
      investigate the functional consequences of the promoter polymorphism by observing 
      the effects of the rs57137919A allele on promoter activity, transcription factor 
      binding, gene expression, cholesterol efflux, and apoptosis levels. The results 
      showed that the rs57137919A allele was significantly associated with decreased 
      ABCG1 gene expression possibly due to the impaired ability of protein-DNA 
      binding. ABCG1-mediated cholesterol efflux decreased by 23% with rs57137919 A/A 
      versus the G/G genotype. Cholesterol-loaded macrophage apoptosis was induced 
      2-fold with the A/A genotype compared with the G/G genotype. Proapoptotic genes 
      Bok and Bid mRNA levels were significantly increased in macrophages from the A/A 
      genotype compared with those from the G/G genotype. These findings demonstrated 
      that the ABCG1 promoter rs57137919G>A variant had an allele-specific effect on 
      ABCG1 expression and was associated with an increased apoptosis in 
      cholesterol-loaded macrophages, providing functional evidence to explain the 
      reduced risk for atherosclerosis in subjects with the ABCG1 promoter rs57137919A 
      allele as reported in our previous study.
FAU - Liu, Fang
AU  - Liu F
AD  - Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences and Peking Union Medical College, Beijing, China.
FAU - Wang, Wei
AU  - Wang W
AD  - Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences and Peking Union Medical College, Beijing, China.
FAU - Xu, Yan
AU  - Xu Y
AD  - Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences and Peking Union Medical College, Beijing, China.
FAU - Wang, Yu
AU  - Wang Y
AD  - Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences and Peking Union Medical College, Beijing, China.
FAU - Chen, Lian-Feng
AU  - Chen LF
AD  - Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences and Peking Union Medical College, Beijing, China.
FAU - Fang, Quan
AU  - Fang Q
AD  - Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences and Peking Union Medical College, Beijing, China.
FAU - Yan, Xiao-Wei
AU  - Yan XW
AD  - Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences and Peking Union Medical College, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140627
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (ABCG1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (BH3 Interacting Domain Death Agonist Protein)
RN  - 0 (BID protein, human)
RN  - 0 (BOK protein, human)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Messenger)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
EIN - PLoS One. 2014;9(9):e108083
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/*genetics/metabolism
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - *Apoptosis
MH  - Atherosclerosis/*genetics
MH  - BH3 Interacting Domain Death Agonist Protein/genetics/metabolism
MH  - CHO Cells
MH  - Cell Line, Tumor
MH  - Cholesterol/pharmacology
MH  - Cricetinae
MH  - Cricetulus
MH  - Female
MH  - HEK293 Cells
MH  - Hep G2 Cells
MH  - Humans
MH  - Macrophages/drug effects/*metabolism
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Single Nucleotide
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
PMC - PMC4074052
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/06/28 06:00
MHDA- 2015/10/27 06:00
PMCR- 2014/06/27
CRDT- 2014/06/28 06:00
PHST- 2014/02/10 00:00 [received]
PHST- 2014/04/14 00:00 [accepted]
PHST- 2014/06/28 06:00 [entrez]
PHST- 2014/06/28 06:00 [pubmed]
PHST- 2015/10/27 06:00 [medline]
PHST- 2014/06/27 00:00 [pmc-release]
AID - PONE-D-14-06281 [pii]
AID - 10.1371/journal.pone.0097044 [doi]
PST - epublish
SO  - PLoS One. 2014 Jun 27;9(6):e97044. doi: 10.1371/journal.pone.0097044. eCollection 
      2014.