Polymorphism of stromal cell-derived factor-1 selectively upregulates gene expression and is associated with increased susceptibility to coronary artery disease |
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Authors: | Xiao-Long Gu Na Ma Ding-Cheng Xiang Jun Huang Zheng-Hua Dong Hui-Yan Lei Ru Ding Zhi-Hua Gong Yan-Fei Wen Jian Qiu Lan Ma |
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Affiliation: | 1. Graduate School, Southern Medical University, Guangzhou 510515, China;2. Department of Cardiology, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, China;3. Department of Cardiology Hospital, Shanghai 200135, China;4. Department of Ultrasound, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, China;5. Department of Cardiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China;6. Department of Cardiology, East Hospital, Tongji University, Shanghai 200120, China |
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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. |
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Keywords: | SDF-1 Polymorphism Monocytes CD14 CAD |
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