摘要目的 检测APOE、SLCO1B1基因多态性,探讨其与冠心病发病风险及严重程度的相关性.方法 病例对照研究连续募集2017年3月至11月期间,在北京大学人民医院心血管内科就诊的疑似冠心病患者1267例,经冠脉造影及纳排标准筛选后,最终入选冠心病患者391例为病例组、非冠心病患者223例为对照组,应用Gensini评分对冠心病患者严重程度进行评估.Real-time PCR法检测APOE(388T>C,526C>T)、SLCO1B1(388A>G,521T>C)位点突变,并采用Sanger测序法验证.结合环境因素,探讨APOE和SLCO1B1基因多态性与冠心病发病风险、病情严重程度的关系.结果 两种方法检测APOE、SLCO1B1基因多态性的结果符合率为100％,二者基因分布均符合Hardy-Weinberg平衡.APOE在病例组和对照组中,均以 ε3/ε3基因型和 ε3等位基因最为常见,分别为 ε3/ε3(70.8％,73.1％)、ε3(83.5％,85.2％);APOE各基因型及等位基因在两组间差异无统计学意义(P>0.05);ε4+在病例组Gensini≥72的亚组中分布比例较高(P<0.05).SLCO1B1在病例组和对照组中均以基因型*1b/*1b和等位基因*1b比例最高,分别为*1b/*1b(37.3％vs 36.8％)、*1b(60.1％vs 61.7％).SLCO1B1基因型及等位基因频率分布在两组间及不同冠心病疾病严重程度亚组间比较,差异均无统计学意义(P>0.05).结论 本研究未发现APOE和SLCO1B1基因多态性与冠心病发病风险有关,但APOEε4+可能增加冠心病的疾病严重程度.

abstractsObjective The single nucleotide polymorphisms (SNPs) of APOE and SLCO1B1 were examined to explore their association with the risk and severity of coronary heart disease(CAD). Methods A total of 1267 cases of consecutive coronary heart disease (CAD)-suspected inpatients visiting department of Cardiology in Peking University Peoples' Hospital from March 2017 to november were recruited into this case-control study, and then 391 CAD cases and 223 non-CAD controls were enrolled for final analysis after screening by coronary angiography and exclusion criteria. The severity of the CAD cases were evaluated according to Gensini scores. The SNPs of APOE(388T>C, 526C>T) and SLCO1B1(388A>G, 521T>C) were detected using Real-time PCR and further verified using Sanger sequencing. Environmental risk factors were collected, and the correlations between SNPs of APOE and SLCO1B1 and the risk and severity of CAD were performed by SPSS version 16.0. Results The SNPs of all the subjects included in CAD group and non-CAD group were successfully detected, with an accordance of 100％ to Sanger sequencing. The distribution of APOE and SLCO1B1 gene were subjected to Hardy-Weinberg. The&nbsp;distributions of APOE gene ε3/ε3 genotypes and ε3 allele were most commonly found in both CAD group and non-CAD group (ε3/ε3: 70.8％,73.1％;ε3: 83.5％,85.2％;respectively). APOE genotypes and alleles were comparable between the CAD cases and non-CAD controls (P>0.05). The frequencies of APOE gene ε4+genotype were more likely to be found in the subgroup of CAD with Gensini score≥72 (P<0.05). The distributions of SLCO1B1 gene *1b/*1b genotypes and *1b allele were most commonly found in both CAD group and non-CAD group (*1b/*1b: 37.3％, 36.8％; *1b: 60.1％, 61.7％; respectively). There was no significant difference in genotype and allele frequencies of SLCO1B1 between the two groups and among subgroups with different severity of CAD (P>0.05). Conclusion This study observed no association between SNPs of APOE, SLCO1B1 and the risk of CAD in this population. However, APOE gene ε4 +genotype may increase the severity of CAD.