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.

Keywords: CAD; CD14; Monocytes; Polymorphism; SDF-1.