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浙江大学学报（医学版）
J Zhejiang Univ (Med Sci)  2018, Vol. 47 Issue (5): 514-519    DOI: 10.3785/j.issn.1008-9292.2018.10.11
    
Association of CXCL12/CXCR4 gene polymorphisms with genetic risk and severity of coronary stenosis in patients with coronary artery disease
WANG Anqi(),LIU Xinyue*()
Department of Clinical Laboratory, Second Hospital of Lanzhou University, Lanzhou 730030, China
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Abstract  

Objective: To investigate the association of CXCL12 and CXCR4 polymorphisms with the genetic risk and severity of coronary stenosis in patients with coronary artery disease (CAD). Methods: Competitive allele specific PCR(KASP) was performed to identify the genotypes of rs2297630 and rs2322864 polymorphisms in 302 CAD patients and 302 age-and gender-matched healthy controls. The severity of CAD patients was assessed by the Gensini scoring system according to the results of coronary arteriography. The association of rs2297630 and rs2322864 polymorphisms with genetic risk of CAD and Gensini scores were analyzed by unconditional logistic regression and multivariate linear regression respectively. Results: There were significant differences in the genotype and allele frequencies of both rs2297630 and rs2322864 between the CAD group and healthy control (all P < 0.01). Regression analysis showed that rs2297630 polymorphism was associated with genetic risk of CAD and Gensini scores (all P < 0.01). People who carried the AA genotype suffered higher risk of CAD susceptibility and more serious coronary stenosis (all P < 0.01), compared with GG genotype carriers. There was also significant association between rs2322864 polymorphism and genetic risk of CAD (P < 0.01); those who carried the CT genotype had higher risk of CAD (P < 0.01), compared with TT genotype carriers. However, rs2322864 polymorphism was not associated with the severity of coronary stenosis (P>0.05). Conclusions: Gene polymorphism of CXCL12 rs2297630 is associated with the genetic risk of CAD and the severity of coronary stenosis. Moreover, the gene polymorphism of CXCR4 rs2322864 is associated with genetic risk of CAD, but not with the severity of coronary stenosis.

Key words： Coronary disease/etiology      Coronary disease/genetics      Coronary stenosis/etiology      Coronary stenosis/genetics      Receptors, chemokine      Chemokine CXCL12      Alleles      Genotype      Polymorphism, genetic     
Received: 12 September 2018      Published: 23 January 2019
CLC:  R541.4  
Corresponding Authors: LIU Xinyue     E-mail: 18793189325@163.com;liuxy@lzu.edu.cn
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Cite this article:

WANG Anqi,LIU Xinyue. Association of CXCL12/CXCR4 gene polymorphisms with genetic risk and severity of coronary stenosis in patients with coronary artery disease. J Zhejiang Univ (Med Sci), 2018, 47(5): 514-519.

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http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2018.10.11     OR     http://www.zjujournals.com/med/Y2018/V47/I5/514


CXCL12及CXCR4基因多态性与冠心病发病风险和冠状动脉狭窄程度的相关性

目的: 探究甘肃省汉族人群CXC型趋化因子配体12（CXCL12）及其受体趋化因子受体4（CXCR4）rs2297630和rs2322864位点基因多态性与冠心病发病风险以及冠状动脉狭窄程度的相关性。方法: 2017年11月至2018年6月在兰州大学第二医院住院治疗的302例无血缘关系的冠心病患者作为冠心病组，同期年龄、性别相匹配的302名无血缘关系的体检者作为健康对照组。应用竞争性等位基因特异性PCR法检测所有研究对象rs2297630和rs2322864位点的基因分型，并根据冠状动脉造影结果采用Gensini评分对患者冠状动脉狭窄程度进行评价。采用二元Logistic回归分析和多因素线性回归分析rs2297630和rs2322864基因多态性与冠心病发病风险和冠状动脉狭窄程度的相关性。结果: 冠心病组与健康对照组rs2297630和rs2322864等位基因和基因型分布频率差异均具有统计学意义（均P < 0.01）；rs2297630与冠心病的发病风险和冠状动脉病变狭窄程度均相关（均P < 0.01），AA基因型者冠心病的发病风险和冠状动脉狭窄严重程度增加（均P < 0.01）。rs2322864与冠心病的发病风险相关（P < 0.01），CT基因型会增加冠心病的发病风险（P < 0.01），但与冠状动脉狭窄程度不相关（P>0.05）。结论: 甘肃省汉族人群中CXCL12多态性位点rs2297630与冠心病的发病风险和冠状动脉狭窄程度相关，其受体CXCR4上的常见突变位点rs2322864也与冠心病的发病风险相关，但与冠状动脉狭窄程度不相关。


关键词： 冠心病/病因学,  冠心病/遗传学,  冠状动脉狭窄/病因学,  冠状动脉狭窄/遗传学,  受体, 趋化因子,  趋化因子CXCL12,  等位基因,  基因型,  多态现象, 遗传 
[${\bar x}$±s或n(%)]
组别 n 男性 年龄(岁) 血糖(mmol/L) 总胆固醇(mmol/L) HDL(mmol/L) 三酰甘油(mmol/L) LDL(mmol/L) 高血压 糖尿病
  与健康对照组比较，**P＜0.01.HDL：高密度脂蛋白胆固醇.LDL:低密度脂蛋白胆固醇.
冠心病组 302 192(63.6) 62±9 7.0±3.0** 4.3±1.1** 1.1±0.3** 1.9±1.4** 2.3±0.9 181(59.9)** 82(27.2)**
健康对照组 302 192(63.6) 60±9 5.2±0.7 4.0±0.9 1.2±0.3 1.4±0.6 2.3±0.7 142(47.0) 21(7.0)
Tab 1 Clinical characteristics of the study population
[n(%)]
组别 等位基因 基因型
G A GG AG AA
冠心病组 465(77.0) 139(23.0) 195(64.6) 75(24.8) 32(10.6)
健康对照组 516(85.4) 88(14.6) 223(73.8) 70(23.2) 9(3.0)
χ2值 14.11 14.95
P值 < 0.01 < 0.01
Tab 2 The genotype and allele frequency of CXCL12 rs2297630 between 302 patients with coronary artery disease and 302 healthy controls
[n(%)]
组别 等位基因 基因型
T C TT CT CC
冠心病组 454(75.2) 150(24.8) 162(53.6) 130(43.0) 10(3.3)
健康对照组 497(82.3) 107(17.7) 204(67.5) 89(29.5) 9(3.0)
χ2值 9.14 12.55
P值 < 0.01 < 0.01
Tab 3 The genotype and allele frequency of CXCR4 rs2322864 between 302 patients with coronary artery disease and 302 healthy controls
单核苷酸多态性 遗传模型 单因素分析 多因素分析*
OR(95%CI) P值 OR(95%CI) P值
  *校正了性别、年龄、血糖、总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、高血压、糖尿病等因素.
rs2297630 A:G 等位基因模型 1.753(1.305, 2.354) < 0.01 2.185(1.537, 3.107) < 0.01
AG:GG 共显性模型 1.225(0.839, 1.788) ＞0.05 1.307(0.832, 2.053) ＞0.05
AA:GG 共显性模型 4.066(1.894, 8.730) < 0.01 8.629(3.414, 21.814) < 0.01
AA+AG:GG 显性模型 1.549(1.093, 2.195) ＜0.05 1.797(1.182, 2.733) < 0.01
AA:AG+GG 隐性模型 3.858(1.808, 8.232) < 0.01 7.870(3.164, 19.574) < 0.01
rs2322864 C:T 等位基因模型 1.535(1.161, 2.028) < 0.01 1.599(1.157, 2.209) < 0.01
CT:TT 共显性模型 1.839(1.310, 2.583) < 0.01 1.887(1.265, 2.815) < 0.01
CC:TT 共显性模型 1.399(0.555, 3.525) ＞0.05 1.744(0.625, 4.871) ＞0.05
CC+CT:TT 显性模型 1.799(1.293, 2.503) < 0.01 1.874(1.270, 2.764) < 0.01
CC:CT+TT 隐性模型 1.115(0.447, 2.784) ＞0.05 1.370(0.496, 3.781) ＞0.05
Tab 4 Association of genetic variations of rs2297630 and rs2322864 with risk of coronary artery disease
单核苷酸多态性 遗传模型 单因素分析 多因素分析*
β(95%CI) P值 β(95%CI) P值
  *校正了性别、年龄、血糖、总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、高血压、糖尿病、病变血管数等因素.
rs2297630 A:G 等位基因模型 0.102(0.021, 0.169) ＜0.05 0.071(0.001, 0.132) ＜0.05
AG:GG 共显性模型 0.002(-0.11, 0.12) ＞0.05 -0.004(-0.11, 0.10) ＞0.05
AA:GG 共显性模型 0.161(0.038, 0.225) < 0.01 0.118(0.012, 0.180) ＜0.05
AA+AG:GG 显性模型 0.076(-0.036, 0.183) ＞0.05 0.050(-0.050, 0.147) ＞0.05
AA:AG+GG 隐性模型 0.161(0.040, 0.223) < 0.01 0.118(0.015, 0.179) ＜0.05
rs2322864 C:T 等位基因模型 0.005(-0.071, 0.080) ＞0.05 0.018(-0.049, 0.083) ＞0.05
CT:TT 共显性模型 -0.017(-0.095, 0.128) ＞0.05 0.052(-0.049, 0.150) ＞0.05
CC:TT 共显性模型 -0.011(-0.123, 0.101) ＞0.05 -0.023(-0.122, 0.076) ＞0.05
CC+CT:TT 显性模型 0.014(-0.098, 0.125) ＞0.05 0.044(-0.056, 0.142) ＞0.05
CC:CT+TT 隐性模型 -0.014(-0.124, 0.097) ＞0.05 -0.032(-0.128, 0.066) ＞0.05
Tab 5 Association of genetic variations of rs2297630 and rs2322864 with coronary artery stenosis
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