EP300基因rs20551多态性与缺血性脑卒中痰瘀证和冠心病痰瘀证及其凝血功能的关联研究

Relationship of EP300 gene rs20551 polymorphism with phlegm stasis syndrome and blood coagulation function in CIS and CHD patients

目的探讨EP300基因rs20551多态性与缺血性脑卒中痰瘀证和冠心病痰瘀证的易感性及其临床凝血功能的关联.方法选择缺血性脑卒中痰瘀证患者550例(脑卒中组),冠心病痰瘀证患者550例(冠心病组),另选取同期体检中心健康体检者以及骨科病情轻微患者550例(对照组).检测各组活化部分凝血酶原时间(APTT)、D-二聚体、纤维蛋白原、国际标准化比值、血小板计数(Plt)、凝血酶原时间、凝血酶原时间活动度(PTA)和凝血酶时间(TT),采用RT-PCR技术检测患者外周血EP300基因mRNA表达水平.结果脑卒中组、冠心病组EP300基因mRNA表达明显高于对照组,差异有统计学意义(P=0.000).校正年龄、性别后,脑卒中组EP300基因rs20551多态性与APTT(加性模型:β=-1.83,95%CI:-3.52^-0.13,P=0.035;显性模型:β=-1.89,95%CI:-3.70^-0.07,P=0.042)、PTA(加性模型:β=5.51,95%%CI:1.12-9.89,P=0.014;显性模型:β=5.40,95%CI:0.72~10.09,P=0.024)相关.冠心病组EP300基因rs20551多态性与APTT(隐性模型:β=35.09,95%CI:6.22~63.96,P=0.018)、D-二聚体(隐性模型:β=7.56,95%CI:3.62~11.49,P=0.000)、Plt(加性模型:β=23.40,95%CI:-41.75^-5.05,P=0.013;显性模型:β=-22.10,95%CI:-41.38^-2.82,P=0.025)、TT(加性模型:β=9.11,95%CI:3.40~14.83,P=0.002;隐性模型:β=109.00,95%CI:79.52~138.50,P=0.000)相关.结论 EP300基因表达可能影响缺血性脑卒中痰瘀证、冠心病痰瘀证的发生,且EP300基因rs20551多态性可能对缺血性脑卒中痰瘀证、冠心病痰瘀证的凝血功能都有影响.从一定程度上支持了“异病同证”理论.

Objective To study the relationship of EP300 gene rs20551 polymorphism with phlegm stasis syndrome and blood coagulation function in cerebral ischemic stroke(CIS)and CHD patients. Methods Five hundred and fifty CIS patients with phlegm stasis syndrome served as a CIS group,550 CHD patients with phlegm stasis syndrome served as a CHD group,and 550 healthy persons served as a control group.Their APTT,platelets,PTA,TT were recorded.Their serum D-dimer and fibrinogen levels were measured.The expression of EP300 gene mRNA in three groups was detected by RT-PCR.Results The EP300 gene mRNA expression level was significantly higher in CIS group and CHD group than in control group(P =0.000).The EP300 gene rs20551 polymorphism was related with the APTT and PTA in CIS group(β=-1.83,95%CI:-3.52--0.13,P =0.035;β=-1.89,95%CI:-3.70--0.07,P =0.042;β=5.51,95%CI:1.12- 9.89,P =0.014;β=5.40,95%CI:0.72-10.09,P =0.024)and with the APTT,serum D-dimer level,platelets and TT in CHD group after adjustment for age and gender(β=35.09,95%CI: 6.22-63.96,P =0.018;β=7.56,95%CI:3.62-11.49,P=0.000;β=23.40,95%CI:-41.75--5.05,P =0.013;β=23.40,95%CI:-41.75--5.05,P =0.013;β=-22.10,95%CI:-41.38--2.82,P =0.025;β=9.11,95%CI:3.40-14.83,P =0.002;β=109.00,95%CI: 79.52-138.50,P =0.000).Conclusion EP300 gene expression can influence the occurrence of phlegm stasis syndrome and blood coagulation function in CIS and CHD patients,which supports the term in traditional Chinese medicine,namely “different diseases with a same syndrome”.