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骨保护素启动子区域T149C和T 950 C基因多态性及血清骨保护素水平与冠心病的关系

Polymorphisms of T149C and T950C genes in osteoprotegerin promoter sites and the relationship between serum osteoprotegerin levels and coronary heart disease
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摘要 目的探讨骨保护素(OPG)启动子区域T149C、T950C基因多态性及血清OPG、可溶性核转录因子-κB受体活化因子配体(sRANKL)含量与冠心病(CHD)发病风险的关系。方法选择2017年4月至2018年12月天津市胸科医院心内科收治的天津地区疑似CHD入院并接受冠状动脉造影(CAG)的528例患者,根据CAG检查结果将患者分为CHD组(302例)和非CHD组(226例)。记录所有受试对象的性别、年龄、高血压史、CHD家族史、糖尿病、血脂指标等临床资料;采用酶联免疫吸附试验(ELISA)检测血清OPG、sRANKL水平;应用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)技术检测T149C、T950C基因多态性,等位基因进行Hardy-Weinberg遗传平衡检验;采用二分类多因素非条件Logistic回归法分析T149C、T950C基因多态性及血清OPG、sRANKL水平与CHD的关系。结果所有患者均纳入最终分析。CHD组血清OPG水平明显高于非CHD组(μg/L:1.76±0.49比1.47±0.29,P<0.01),血清sRANKL水平明显低于非CHD组(ng/L:342.14±121.38比376.63±108.66,P<0.05)。Logistic回归分析显示,在调整了年龄、性别、血脂指标、糖尿病等因素后,血清OPG升高为发生CHD的独立危险因素〔优势比(OR)=1.995,95%可信区间(95%CI)=1.935~2.066,P=0.012〕。PCR-RFLP检测结果显示,OPG基因启动子区域T149C、T950C均有TT、TC、CC 3种基因型。经Hardy-Weinberg平衡检验,OPG T149C及OPG T950C基因多态性符合Hardy-Weinberg定律,达到遗传平衡,具有群体代表性。非CHD组T149C基因型TT、TC、CC及等位基因T、C的频率分别为53.5%、42.9%、3.6%、75.0%和25.0%,CHD组分别为43.1%、50.3%、6.6%、68.2%和31.8%,两组间基因型和等位基因频率比较差异均有统计学意义(均P<0.05)。Logistic回归分析显示,T149C位点的TC+CC基因型发生CHD的风险是TT基因型的1.86倍(OR=1.86,95%CI=1.24~2.78,P=0.003),提示C等位基因可能为发生CHD的易感基因。非CHD组T950C基因型TT、TC、CC及等位基因T、C的� Objective To explore the polymorphisms of T149C and T950C gene in osteoprotectin (OPG) promoter sites and the levels of serum OPG and soluble nuclear factor-κB receptor activator ligand (sRANKL) and the incidence of coronary heart disease (CHD). Methods 528 patients in Tianjin suspected of CHD and underwent coronary angiography (CAG) who admitted to the department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled. According to the CAG results, they were divided into two groups: CHD group (n = 302) and non-CHD group (n = 226). The gender, age, history of hypertension, family history of CHD, diabetes, levels of blood lipid parameters in serum and other clinical data of patients were recorded. The levels of serum OPG and sRANKL were measured by enzyme-linked immunosorbent assay (ELISA). T149C and T950C gene polymorphisms were analyzed by polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) methods. Hardy-Weinberg genetic balance test was performed for alleles. Binomial classification multivariate non-conditional Logistic regression method was used to analyze the relationship between T149C and T950C gene polymorphisms, serum levels of OPG and sRANKL and CHD. Results All patients were enrolled in the final analysis. The serum level of OPG in CHD group was significantly higher than that in non-CHD group (μg/L: 1.76±0.49 vs. 1.47±0.29, P < 0.01), the serum level of sRANKL was significantly lower than that in non-CHD group (ng/L: 342.14±121.38 vs. 376.63±108.66, P < 0.05). Logistic regression analysis showed that after adjusting for age, gender, blood lipid parameters, diabetes and other factors, the increase in serum OPG level was an independent risk factor for CHD [odds ratio (OR)= 1.995, 95% confidence interval (95%CI)= 1.935-2.066, P = 0.012]. PCR-RFLP results showed that TT, TC and CC genotypes were found in T149C and T950C of OPG promoter. According to Hardy-Weinberg equilibrium test, the polymorphisms of OPG T149C and T950C accorded w
作者 赵福梅 赵辉 张蕊 任珉 刘超 刘珊 马静 宋衍秋 刘婷 张旭 丛洪良 Zhao Fumei;Zhao Hui;Zhang Rui;Ren Min;Liu Chao;Liu Shan;Ma Jing;Song Yanqiu;Liu Ting;Zhang Xu;Cong Hongliang(Tianjin Cardiovascular Institute, Tianjin 300222, China;Department of Cardiology, Tianjin Hospital, Tianjin 300210, China;Department of Cardiology, Tianjin Chest Hospital, Tianjin 300222, China)
出处 《中华危重病急救医学》 CAS CSCD 北大核心 2019年第3期319-324,共6页 Chinese Critical Care Medicine
基金 天津市科技计划项目(16ZXMJSY00140).
关键词 骨保护素 基因多态性 启动子 可溶性核转录因子-κB受体活化因子配体 冠心病 Osteoprotegerin Gene polymorphism Promoter Soluble nuclear factor-κB receptor activator ligand Coronary heart disease
作者简介 通信作者:丛洪良,Email:hongliangcong@126.com.
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