巴彦淖尔地区中老年心脑血管疾病患者载脂蛋白E和SLCO1B1基因多态性分布

Distribution of apolipoprotein E and SLCO1B1 gene polymorphisms in elderly patients with cardiovascular and cerebrovascular disease in Bayannur region

目的探讨巴彦淖尔地区行他汀类药物治疗的中老年心脑血管疾病患者载脂蛋白E(ApoE)和SLCO1B1基因多态性分布情况,为临床提供个体化用药依据。方法选择2018年9月—2019年12月巴彦淖尔市医院门诊及住院行他汀类药物治疗的115例中老年心脑血管疾病患者作为研究对象,采用荧光探针捕获和微测序技术检测ApoE和SLCO1B1基因,并与文献报道的其他地区进行比较;测定所有患者的血脂指标,包括三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、极低密度脂蛋白胆固醇(VLDL-C)。结果共检测到6种ApoE基因型:E2/E2、E2/E3、E2/E4、E3/E3、E3/E4、E4/E4,基因型频率分别为0.87%、6.09%、2.60%、62.61%、26.96%、0.87%;6种SLCO1B1基因型:*1a/*1a、*1a/*1b、*1b/*1b、*1a/*15、*1b/*15、*15/*15,基因型频率为5.22%、31.30%、40.00%、6.09%、16.52%、0.87%。ApoE 2型、3型和4型3种基因表型患者的性别、年龄、TG、TC、HDL-C、VLDL-C水平比较差异均无统计学意义;LDL-C水平依次升高(分别为1.73±0.54、2.58±0.92、2.71±0.86 mmol/L,P<0.05);SLCO1B13组基因表型患者的性别、年龄、血脂指标比较差异均无统计学意义。巴彦淖尔地区ApoE和SLCO1B1基因型分布频率与沈阳和重庆地区比较差异均无统计学意义;巴彦淖尔地区ApoE基因型分布频率与武汉及周边地区比较差异有统计学意义,SLCO1B1基因型分布频率与武汉及周边地区比较差异无统计学意义。结论巴彦淖尔地区中老年心脑血管疾病患者ApoE基因以ApoE3基因表型为主,应用他汀类药物降脂疗效较好。SLCO1B1基因以Ⅱ类基因表型(正常肌病风险)为主,应用他汀类药物不良反应发生率较低。ApoE基因可能存在地区差异,建议患者服用他汀类药物前进行基因检测。

Objective To investigate the distribution of apolipoprotein E(ApoE)and SLCO1B1 gene polymorphisms in elderly patients with cardio-and cerebrovascular diseases treated with statins in Bayannur region,and provide evidence for individualized drug use.Methods The 115 elderly patients with cardio-and cerebrovascular diseases in Bayannur Hospital from September 2018 to December 2019 were selected.The ApoE and SLCO1B1 genes were identified by fluorescence probe capture and microsequencing technology,and compared with other regions reported in literature.The patients'blood lipid levels were measured,including triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and very low density lipoprotein cholesterol(VLDL-C).Results Six genotypes of ApoE were detected:E2/E2,E2/E3,E2/E4,E3/E3,E3/E4,E4/E4,with the genotypic frequencies of 0.87%,6.09%,2.60%,62.61%,26.96%,0.87%;6 genotypes of SLCO1B1 were detected:*1a/*1a,*1a/*1b,*1b/*1b,*1a/*15,*1b/*15,*15/*15,with genotypic frequencies of 5.22%,31.30%,40.00%,6.09%,16.52%,0.87%.There were no significant differences in gender,age,TG,TC,HDL-C and VLDL-C in ApoE2,ApoE3,ApoE4 gene phenotype groups,and LDL-C was increasing(1.73±0.54,2.58±0.92,2.71±0.86 mmol/L,P<0.05).There was no significant differences in sex,age and lipid levels among the three phenotype groups of SLCO1B1.There was no significant difference in ApoE and SLCO1B1 genotypes between Bayannur and Shenyang,Chongqing regions.ApoE genotype in Bayannur region was significantly different from that in Wuhan and surrounding area,while SLCO1B1 genotype was not significantly different from that in Wuhan and surrounding area.Conclusions ApoE gene of elderly patients with cardio-and cerebrovascular disease in Bayannur region is mainly ApoE3,with a good effect on reducing blood lipid.SLCO1B1 gene is mainlyⅡphenotype with normal risk of myopathy and relatively low incidence of adverse reactions.There may be regional differences in ApoE gene,so patients should carry out gene detection before taking statins.