PCSK9基因rs662145位点多态性与冠状动脉粥样硬化性心脏病血脂的关系

Relationship between rs662145 polymorphism of PCSK9 gene and blood lipid in patients with coronary atherosclerotic heart disease

目的探讨PCSK9基因rs662145位点多态性与冠状动脉粥样硬化性心脏病(coronary atherosclerotic heart disease,CHD)的关系,并观察他汀在PCSK基因rs662145位点不同基因型中调脂效果的差异。方法选取行CAG检查的福建汉族患者261例,根据CAG结果分为CHD组和对照组,收集患者的基本资料并留取空腹血标本,测定TG、TC、LDL-C等血脂指标,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测PCSK9基因rs662145位点多态性,并在完成随访的57例患者复测相应血脂指标。结果 CHD组rs662145位点C等位基因频率为20.59%,高于对照组的10.53%(χ~2=6.011,P=0.019);CC、CT、TT基因型频率在两组间分布差异也有统计学意义(χ~2=9.418,P=0.007);含C等位基因CHD组患者TC及LDL-C水平更高(CC>CT>TT,P<0.05),但HDL-C较低(CC<CT<TT,P<0.05)。CHD组患者血浆TC、HDL-C、LDL-C、ApoA水平在CC、CT、TT基因型亚组间的差异有统计学意义(P<0.05),对照组血脂水平在各基因型亚组间的差异无统计学意义(P>0.05)。CHD患者经过他汀治疗后,血浆TG、TC及LDL-C水平均较前降低,HDL-C水平较前升高(P<0.05),但CC、CT、TT各基因型患者经他汀治疗前后血脂变化值差异无统计学意义(P>0.05)。结论 PCSK9基因rs662145位点多态性与福建汉族冠心病人群血脂异常有关,rs662145位点C等位基因可能是冠心病高风险突变位点。

Objective To explore the relationship between rs662145 polymorphism of PCSK9 gene and blood lipid in patients with coronary atherosclerotic heart disease,and to compare the efficacy of statins in various PCSK9 rs662145 genotypes in patients with coronary atheroscleroticheart disease.Methods A total of 261 patients undergoing coronary angiography were divided into CHD group(n=204) and control group(n=57).Basic information,fasting glucose,total triglyceride(TG), total cholesterol(TC) and low density lipoprotein cholesterol(LDL-C)and other lipid profiles were tested immediately after admission.Genotyping of PCSK9 polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method.Lipid profile was redetermined in patients who had accepted statins for three months and completed the follow-up.Results The frequency of C allele was 20.59% in CHD group,which was higher than 10.53% in the control group(χ^2=6.011,P=0.019).The distribution of PCSK9 rs662145 genotype(CC,CT,TT) among two groups showed statistically significant difference(χ^2=9.418,P=0.007).Patients with C allele in CHD group had higher levels of TC and LDL-C but lower HDL-C levels(P<0.05).TC,HDL-C,LDL-C and ApoA levels also demonstrated statistically significant difference between three genotypes(CC,CT and TT) in the CHD group(P<0.05),meanwhile no difference was seen in the lipid profiles of the control group among three genotypes.TG,TC and LDL-C levels decreased with the elevation of HDL-C after three months treatment with statins in CHD group(P<0.05).No significant differences were observed in the variation of lipid profile after treatment with statins among three genotypes(CC,CT,TT)(P>0.05).Conclusion PCSK9 gene rs662145 polymorphism was associated with lipid levels in CHD patients among Fujian Han population.C allele may increase the risk of the onset of coronary heart disease.