2020 年第 12 期 第 15 卷

北京地区汉族人群溶质载体有机阴离子转运蛋白家族1B1与载脂蛋白E基因多态性分布及其意义

Distribution and clinical significance of polymorphism of solute carrier organic anion transporter family member 1B1 and apolipoproteins E gene in Beijing Han population 

作者：王燕1陈思1袁慧1曾小莉1崔颖2

英文作者：Wang Yan1 Chen Si1 Yuan Hui1 Zeng Xiaoli1 Cui Ying2

单位：1首都医科大学附属北京安贞医院检验科100029；2北京市第一社会福利院北京市老年病医院检验科100011

英文单位：1Department of Laboratory Beijing Anzhen Hospital Capital Medical University Beijing 100029 China; 2Department of Laboratory the First Social Welfare Instiution of Beijing Beijing Geriatric Hospital Beijing 100011 China

关键词：他汀类药物；溶质载体有机阴离子转运蛋白家族1B1；载脂蛋白E；基因多态性

英文关键词：Statins;Solutecarrierorganicaniontransporterfamilymember1B1;ApolipoproteinsE;Genepolymorphism

• 摘要：

• 目的 探讨北京地区汉族人群溶质载体有机阴离子转运蛋白家族1B1（SLCO1B1）与载脂蛋白E（ApoE）基因多态性分布及其临床意义。方法连续入选2019年7月至2020年1月首都医科大学附属北京安贞医院住院和门诊患者以及健康检查志愿者8 132例，采用聚合酶链反应荧光探针法检测SLCO1B1（rs2306283：388 A>G，rs4149056：521 T>C）及ApoE（rs429358：388 T>C，rs7412：526 C>T）多态性位点，分析基因多态性分布情况，分别比较不同性别和不同年龄分层人群SLCO1B1与ApoE基因多态性分布、基因型分布及多态性位点突变频率的差异。结果 北京地区汉族人群中共检出SLCO1B1基因8种表型，*5/*5未检测到，*1a/*1a、*1a/*1b、*1b/*1b、*1a/*5、*1a/*15、*1b/*15、*5/*15和*15/*15检出者分别为567例（6.97%）、2 619例（32.21%）、3 241例（39.85%）、3例（0.04%）、473例（5.82%）、1 128例（13.87%）、2例（0.02%）和99例（1.22%）。根据服用他汀类药物后发生横纹肌溶解症或肌病的风险及服用药物的剂量分为正常代谢型、中间代谢型和弱代谢型，占比分别为79.03%（6 427/8 132）、19.72%（1 604/8 132）和1.24%（101/8 132）。北京地区汉族人群中共检出ApoE基因6种不同表型，ε2/ε2、ε2/ε3、ε2/ε4、ε3/ε3、ε3/ε4和ε4/ε4检出者分别为45例（0.55%）、956例（11.76%）、107例（1.32%）、5 616例（69.06%）、1 331例（16.37%）、77例（0.95%）。根据不同基因型发生冠状动脉粥样硬化性心脏病、脑梗死、阿尔茨海默病等的风险及服用他汀类药物的疗效将其分为三大类，ApoE保护类基因型、ApoE大众类基因型和ApoE风险类基因型，占比分别为12.31%（1 001/8 132）、70.38%（5 723/8 132）和17.31%（1 408/8 132）。同时具有ApoE保护类基因型和SLCO1B1正常代谢型患者796例(9.79%)，同时具有ApoE风险类基因型和SLCO1B1弱代谢型患者23例(0.28%)。在男性和女性人群以及年龄≤60岁和>60岁人群中，SLCO1B1均以正常代谢型占比最高，ApoE均以大众类基因型占比最高，不同性别和不同年龄分层人群SLCO1B1和ApoE基因型分布情况差异均无统计学意义(均P>0.05)。SLCO1B1及ApoE基因的上述多态性位点突变频率观察值符合Hardy-Weinberg遗传平衡（P>0.05），具有群体代表性。结论 本研究具有群体代表性，北京地区汉族人群SLCO1B1和ApoE基因多态性与性别和年龄分层无关，根据基因型及时调整他汀类药物用药方案，有助于实现个体化用药和安全用药。

• Objective To explore the distribution and clinical significance of solute carrier organic anion transporter family 1B1(SLCO1B1) and apolipoproteins E (ApoE) gene polymorphisms in Beijing Han population. Methods From July 2019 to January 2020, 8 132 inpatients，outpatients and health examination volunteers  in Beijing Anzhen Hospital， Capital Medical University were enrolled. The SLCO1B1 (rs2306283:388 A>G, rs4149056:521 T>C) and ApoE (rs429358:388 T>C, rs7412:526 C>T) polymorphism sites were detected by polymerase chain reaction （PCR）fluorescent probe method, and the distribution of gene polymorphism was analyzed. The distribution of SLCO1B1 and ApoE genotypes and the mutation frequency of polymorphic loci were compared between different genders and different age groups. Results Totally 8  phenotypes of SLCO1B1 gene were detected in Beijing Han population, and *5/*5 was not detected. The 8 phenotypes of SLCO1B1 (*1a/*1a, *1a/*1b, *1b/*1b, *1a/*5, *1a/*15, *1b/*15, *5/*15 and *15/*15) were 567 cases(6.97%), 2 619 cases (32.21%), 3 241 cases (39.85%), 3 cases (0.04%), 473 cases (5.82%), 1 128 cases (13.87%), 2 cases (0.02%) and 99 cases (1.22%). According to the risk of rhabdomyolysis or myopathy after taking statins and the dosage of the drug, they could be divided into the normal metabolism， the intermediate metabolism and the low metabolism, which were 79.03%（6 427/8 132）， 19.72%（1 604/8 132） and 1.24%（101/8 132）. The frequencies of 6 phenotypes of ApoE were ε2/ε2 ［45 cases (0.55%)］,ε2/ε3［956 cases (11.76%)］,ε2/ε4［107 cases (1.32%)］,ε3/ε3［5 616 cases (69.06%)］,ε3/ε4［1 331 cases (16.37%)］ and ε4/ε4［77 cases (0.95%)］. According to the risk of coronary heart disease, cerebral infarction and Alzheimer′s disease of different genotypes and the effect of taking statins, they were divided into three categories: ApoE protective genotype, ApoE popular genotype and ApoE risk genotype, which were 12.31%（1 001/8 132）, 70.38%（5 723/8 132） and 17.31%（1 408/8 132）.Total of 796 patients (9.79%) had both ApoE protected genotype and SLCO1B1 normal metabolism, and 23 patients (0.28%) had both ApoE risk genotype and SLCO1B1 low metabolism. In both male and female populations, as well as in those aged ≤60 years and >60 years, SLCO1B1 accounted for the highest proportion of normal metabolic type, while ApoE accounted for the highest proportion of general genotype. There were no statistically significant differences in SLCO1B1 and ApoE genotype distribution between different genders and between different age groups (both P>0.05). The observed values of the mutation frequency of the above-mentioned polymorphic sites of SLCO1B1 and ApoE genes were consisted with the Hardy-Weinberg genetic balance (P>0.05), which was representative of the population. Conclusion sSLCO1B1 and ApoE gene polymorphism are not related to gender and age stratification in the Han population in Beijing. Timely adjustment of statin regimen according to genotype is helpful to realize individualized and safe medication.