骨形成蛋白2基因多态性与冠脉钙化相关性研究

Correlation between bone morphogenetic protein 2 gene polymorphism and coronary artery calcification

摘要:

目的 研究骨形成蛋白2（bone morphogenetic protein 2，BMP2）基因多态性在重庆汉族人群中的分布及与冠脉钙化（coronary artery calcification，CAC）的相关性。方法 收集2019年3月至2019年5月260例重庆医科大学附属第一医院心内科重庆汉族冠脉造影患者临床资料及血液样本，通过测序检测患者BMP2 rs961253、rs235768、rs1049007，OPG rs2073617、rs2073618， S100A12 rs2916191基因位点序列，应用ELISA法检测血清BMP2、OPG、S100A12水平。结果 CAC组167例，年龄（67.13±9.64）岁；对照组93例，年龄（60.46±9.89）岁。高血压、糖尿病、肥胖患者更容易发生CAC，CAC组男性发病率、载脂蛋白A1、C反应蛋白、白细胞数以及血清BMP2、S100A12、OPG水平明显高于对照组（P<0.05）。BMP2 rs961253基因型频率及等位基因频率分布在CAC组和对照组之间有统计学差异（P<0.05）。钙化组中，BMP2 TT基因型血清BMP2水平明显高于非TT型（P<0.05）。通过校正性别、年龄、体质指数、高血压、糖尿病等影响因素后，多因素逐步logistic回归分析发现BMP2 rs961253 TT基因型人群患CAC风险较高。结论 血清BMP2水平可作为预测CAC的指标之一。BMP2 rs961253基因多态性与CAC显著相关，BMP2 rs961253 T等位基因或TT基因型是CAC的高危因素。

Abstract:

Objective To investigate the distribution of bone metabolic-related gene polymorphism，such as bone morphogenetic protein 2（BMP2），in the Chongqing Han population and its correlation with coronary artery calcification（CAC）.Methods Clinical data and blood samples were collected from patients with coronary angiography in the Department of Cardiology，The First Affiliated Hospital of Chongqing Medical University from March 2019 to May 2019. The detection of BMP2 rs961253，rs235768，rs1049007；OPG rs2073617，rs2073618 and S100A12 rs2916191 gene were taken into direct sequencing. Serum levels of BMP2，OPG and S100A12 were detected by ELISA.Results There were 167 cases in CAC group，with age of （67.13±9.64） years，and 93 cases in control group，with age of （60.46±9.89） years. Patients with hypertension，diabetes and obesity were more likely to develop CAC. The male morbidity，apolipoprotein A1，C-reactive protein，white blood cell count，serum BMP2，S100A12 and OPG levels in CAC group were significantly higher than those in control group（P<0.05）. The genotype frequency and allele frequency distribution of BMP2 rs961253 were significantly different between CAC group and control group（P<0.05）. In CAC group，the serum BMP2 level of BMP2 TT genotype was significantly higher than that of non TT genotype（P<0.05）. After adjusting gender，age，body mass index，hypertension and diabetes，multivariate stepwise logistic regression analysis found that people with BMP2 rs961253 TT genotype had higher risk of CAC.Conclusion The serum level of BMP2 can be regarded as one of the prediction indicators for CAC. BMP2 rs961253 gene polymorphism is significantly associated with CAC，and BMP2 rs961253 T allele or TT genotype is a high risk factor for CAC.