核心蛋白聚糖基因rs7441多态性与缺血性脑卒中痰瘀证、冠心病痰瘀证的遗传关联分析

Association Analyses between Decorin Gene rs7441 Polymorphism and Phlegm-blood Stasis Syndrome of Ischemic Stroke and Coronary Atherosclerotic Heart Disease

目的旨在探讨核心蛋白聚糖(decorin,DCN)基因rs7441多态性与缺血性脑卒中(ischemic stroke,IS)痰瘀证、冠心病(coronary atherosclerotic heart disease,CHD)痰瘀证的遗传关联。方法纳入IS痰瘀证患者、CHD痰瘀证患者、对照组各550例,运用实时荧光定量PCR(qRT-PCR)方法检测DCN基因mRNA外周血表达水平,采用Sequenom MassARRAY技术进行基因分型,通过PLINK、SPSS软件进行统计分析。结果①DCN基因在IS痰瘀证患者、CHD痰瘀证患者外周血中的mRNA表达水平均显著低于对照组(均P<0.001)。②DCN基因外周血mRNA表达水平与IS痰瘀证患者的空腹血糖(FPG)、活化部分凝血酶原时间(APTT)、国际标准化比值(INR)、凝血酶原时间(PT)、凝血酶原时间活动度(PTA)的相关性均具有统计学意义(均P<0.05),与CHD患者收缩压(SBP)、舒张压(DBP)也显著相关(均P<0.050)。③DCN基因rs7441多态性与IS痰瘀证、CHD痰淤证的发生风险的关联无统计学意义(均P>0.050)。④DCN基因rs7441多态性与IS痰瘀证患者的血清载脂蛋白B(APO-B)(加性模型:Padj=0.006)、低密度脂蛋白(LDL)(加性模型:Padj=0.029)水平显著相关,rs7441多态性与CHD痰瘀证患者的国际标准化比值(INR)显著关联(加性模型:Padj=0.018)。结论DCN基因mRNA表达水平可能参与IS痰瘀证、CHD痰瘀证的发生,rs7441多态性可能影响IS痰瘀证患者的血脂代谢、CHD痰瘀证患者的凝血功能。

Objective To explore the genetic association between the Decorin(DCN)gene rs7441 polymorphism and phlegm-blood stasis syndrome of ischemic stroke(IS)and coronary atherosclerotic heart disease(CHD).Methods Totally 550 IS patients with phlegm-blood stasis syndrome,550 CHD patients with phlegm-blood stasis syndrome and 550 controls were enrolled in this study.Real-time quantitative PCR(qRT-PCR)was used to detect the DCN mRNA expression levels in IS patients with phlegm-blood stasis syndrome,CHD patients with phlegm-blood stasis syndrome and controls.DCN gene rs7441 polymorphism was genotyping by Sequenom MassARRAY.PLINK and SPSS software were used for statistical analyses.Results(1)DCN mRNA expression levels in IS patients with phlegm-blood stasis syndrome and CHD patients with phlegm-blood stasis syndrome were significantly lower than that in controls(both P<0.001).(2)DCN mRNA expression levels in IS patients with phlegm-blood stasis syndrome were significantly associated with fasting blood glucose(FPG),activated partial prothrombin time(APTT),international normalized ratio(INR),prothrombin time(PT)and prothrombin time activity(PTA)(all P<0.05).Besides,DCN mRNA expression levels in CHD patients with phlegm-blood stasis syndrome were significantly associated with systolic blood pressure(SBP)and diastolic blood pressure(DBP)(both P<0.05).(3)There was no significant association was found between the DCN gene rs7441 polymorphism and the risk of phlegm-blood stasis syndrome of IS and CHD(both P>0.05).(4)Significant differences were found between DCN gene rs7441 polymorphism and serum apolipoprotein B(APO-B)(additive model:Padj=0.006),low density lipoprotein(LDL)(additive model:Padj=0.029)in IS patients with phlegm-blood stasis syndrome.Meanwhile,the rs7441 polymorphism was also found to be significantly associated with the international normalized ratio(INR)in CHD patients with phlegm-blood stasis syndrome(additive model:Padj=0.018).Conclusions The DCN mRNA expression level may be involved in the pathogenesis of phlegm-blood stasis syndrome of IS and CHD.The rs7441 polymorphism may affect the lipid metabolism in IS patients with phlegm-blood stasis syndrome,and the coagulation function in CHD patients with phlegm-blood stasis syndrome.