冠心病患者E-选择素第四外显子基因多态性研究

摘要

目的 探讨冠心病患者E-选择素(E-selectin)第4外显子A561C基因多态性的分布情况,比较不同冠心病类型间血脂水平以及血清半胱氨酸水平的变化情况.方法 诊治的冠心病患者298例(冠心病组)及其同期健康体检者276例(对照组)为研究对象,采用双抗体夹心法检测冠心病组和健康对照组血清可溶性E-选择素表达水平,并对冠心病进行分组[急性心肌梗死(AMI)组98例,不稳定性心绞痛(UA)组106例,稳定性心绞痛(SA)组94例]讨论其基因型间血清E-选择素水平的分布情况;采用改良高效液相色谱法(HPLC)测定血浆同型半胱氨酸;同时对298例冠心病患者和276例健康对照者的E-选择素基因多态性分布情况进行检测,用生化技术检测血脂水平[总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、载脂蛋白A(Apo-A)、载脂蛋白B(Apo-B)].结果 E-选择素A561C基因型在2组分布差异有统计学意义(P<06.05),AC基因型者患冠心病的风险是AA基因型的2.028倍(95%CI=1.036~4.736),C等位基因频率高于A等位基因,差异有统计学意义(P=0.057,Or=1.945,95%CI=1.020~4.374);冠心病组与对照组E-选择素A561C各基因型间血清TC、TG、HDL-C比较差异有统计学意义(P<0.05),而LDL-C、ApoA、ApoB血清学水平比较,差异均无统计学意义(P>0.05),但血脂水平的趋势在AC与AA基因型呈现明显升高水平;各冠心病组与对照组在年龄分布、高血压发生率、TC显著增高(P<0.05),其余指标差异无统计学意义(P>0.05),而血浆Hcy显著增高(P<0.01).急性心肌梗死组、不稳定心绞痛组与对照组比较,血浆Hcy显著增高(P<0.05).结论 E-选择素A561 C基因多态性与冠心病的发病有关联,并可影响血脂和Hcy水平;C等位基因可能是北方汉族地区冠心病发病的遗传易感基因.%Objective To investigate the distribution of E-selectin fourth exon A561C polymorphism in patients with coronary heart disease ( CHD ) , and to compare the changes of serum lipid levels and serum homocysteine levels among different coronary heart disease types .Methods A total of 298 patients with CHD ( CHD group ) who were treated in our hospital from January 2015 to April2017 and 276 healthy subjects ( control group ) were enrolled in the study .The expression levels of serum soluble E selectin were detected by double antibody sandwich method for both groups .Moreover the CHD group was redivided into acute myocardial infarction group (AMI group,n =98), unstable angina group (UA group,n =106), stable angina group (SA group,n=94),then the distribution state of E-selectin gene polymorphism was analyzed for all the subjects.Moreover the plasma levels of homocysteine were detected by modified high performance liquid chromatography (HPLC),meanwhile, the levels of blood fat including TC ,TG,HDL ,LDL,Apo-A,Apo-B were detected by biochemistry assay . Results There was a significant difference in the distribution of E selectin A 561C genotype between CHD group and control group (χ2 =5.885,P<0.05),and the risk of CHD in patients with AC genotype was 2.028 times as high as that in patients with AA genotype (95%CI=1.036~4.736).The frequency of C allele was significantly higher than that of A allele .There were significant differences in the serum levels of TC ,TG,HDL-C among E-selectin A561C genotypes between the two groups (P<0.05),however,there were no significant differences in the serum levels of LDL -C,ApoA,ApoB between two groups (P>0.05), but the blood lipid levels were increased in AC and AA genotypes .The age distribution,incidence rate of hypertension,TC levels and plasma levels of Hcy were significantly increased in CHD group , however,there were no significant differences in the other indexes between two groups (P>0.05).Moreover the plasma levels of Hcy in AMI group and UA group were significantly increased ,as compared with those in control group (P<0.05).Conclusion The E-selectin A 561 C polymorphism is closely correlated to pathogenesis of CHD ,which may influence the levels of blood lipid and Hcy ,moreover , C allele may be a heredity predisposing gene of pathogenesis of CHD in Han people area of north China .