title: Polymorphism of stromal cell-derived factor-1 selectively upregulates gene expression and is associated with increased susceptibility to coronary artery disease.
abstract: Stromal cell-derived factor-1 (SDF-1) plays critical roles in vascular development and hematopoiesis. Here, we investigated the function of SDF-1 rs1801157G/A polymorphism in various immune cells and examined its association with susceptibility to coronary artery disease (CAD). Protein and mRNA levels of SDF-1 were tested in peripheral CD4+ T cell, CD8+ T cells, monocytes, and natural killer (NK) T cells from healthy donors with different genotypes of rs1801157G/A polymorphism. Prevalence of the polymorphism was compared between CAD patients and healthy controls. Data revealed that SDF-1 mRNA and protein were detectable in CD4+ T cells, CD8+ T cells, monocytes and NK T cells. Interestingly, both protein level and mRNA level of SDF-1 were significantly increased in the monocytes with rs1801157AA genotype, whereas the same phenomenon was not observed in the other three cell types. Blockage of CD14 completely inhibited the upregulation of SDF-1 in the monocytes with rs1801157AA genotype. Association analysis showed that frequencies of the rs1801157AA genotype and A allele were significantly higher in CAD cases than in controls (odds ratio [OR]=2.28, 95% confidence interval [CI], 1.50-3.29, p<0.0001, and OR=1.46, 95% CI, 1.21-3.73, p<0.0001, respectively). Also, prevalence of rs1801157AA genotype was further increased in cases with ST-elevation myocardial infarction (OR=1.65, 95% CI, 1.04-2.56, p=0.028). Our data suggest a novel pathway for regulating SDF-1 and a new risk factor for CAD.
authors.affiliation: Graduate School, Southern Medical University, Guangzhou 510515, China; Department of Cardiology, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, China. Electronic address: xiaolonggugz@126.com.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Gu
authors.affiliation: Department of Cardiology Hospital, Shanghai 200135, China.
authors.forename: Na
authors.initials: N
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, China.
authors.forename: Ding-Cheng
authors.initials: DC
authors.lastname: Xiang
authors.affiliation: Graduate School, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Graduate School, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zheng-Hua
authors.initials: ZH
authors.lastname: Dong
authors.affiliation: Department of Ultrasound, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, China.
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: Lei
authors.affiliation: Department of Cardiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Ding
authors.affiliation: Department of Cardiology, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Gong
authors.affiliation: Department of Cardiology, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, China.
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Wen
authors.affiliation: Department of Cardiology, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Cardiology, East Hospital, Tongji University, Shanghai 200120, China. Electronic address: malanseh@126.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D016022:Case-Control Studies; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000378:metabolism; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D013601:T-Lymphocytes / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D019138:Antibodies, Blocking; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger
keywords: CAD; CD14; Monocytes; Polymorphism; SDF-1