孝感地区高脂血症人群ApoE/SLCO1B1基因多态性与血脂水平及他汀类药物相关性研究

Correlation of ApoE/SLCO1B1 gene polymorphisms with lipid levels and statins in hyperlipidemic population in Xiaogan area

目的探讨孝感地区高血脂人群ApoE和SLCO1B1基因位点多态性分布,从分子水平研究该基因不同位点与血脂水平的相关性,评估他汀类药物个体化用药的疗效,为临床高血脂个体化防治提供理论依据。方法选择2022年7月至2023年7月孝感市中心医院900例患者作为研究对象,测定所有患者的血脂指标,包括甘油三酯(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),采用实时荧光定量PCR法定性检测患者外周血全血样本中ApoE基因的ApoE2(526C>T)和ApoE4(388T>C)位点的基因多态性和SLCO1B1基因的SLCO1B1^(*)1b(388A>G)和SLCO1B1^(*)5(521T>C)位点的基因多态性,与国内已报道的其他地区高血脂人群的数据进行比较,分析不同地区间的基因型分布差异。结果血脂异常人群ApoE基因型分布频率为E2/E2(0.34%),E2/E3(14.00%),E3/E3(68.89%),E3/E4(13.22%),E2/E4(1.78%)和E4/E4(1.78%)。SLCO1B1基因型频率:^(*)1a/^(*)1a(7.22%),^(*)1a/^(*)1b(32.89%),^(*)1b/^(*)1b(39.22%),^(*)1a/^(*)5(0.11%),^(*)1a/^(*)15(6.22%),^(*)1b/^(*)15(13.00%),^(*)15/^(*)15(1.33%)。结论孝感地区ApoE中E3/E3基因型所占人数最多,SLCO1B1基因中^(*)1b/^(*)1b型占比最高,即孝感地区高脂血症人群中使用他汀类药物后,大部分人疗效较好,肌病风险较低。ApoE基因型E4基因频率分布与血脂水平差异有统计学意义(P<0.05)。ApoE/SLCO1B1其他位点与血脂水平差异均无统计学意义(P>0.05)。

【Objective】To investigate the polymorphism distribution of ApoE and SLCO1B1 gene loci in hyperlipidemia population in Xiaogan area,study the correlation between different loci of the gene and lipid level from the molecular level,evaluate the efficacy of personalized statin drug administration,and provide theoretical basis for the individualized prevention and treatment of hyperlipidemia.【Methods】Nine hundred patients in Xiaogan Central Hospital from July 2022 to July 2023 were selected as the study objects,and the blood lipid indexes of all patients were determined,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).The polymorphism of ApoE2(526C>T)and ApoE4(388T>C)locus of ApoE gene and SLCO1B1^(*)1b(388A>G)and SLCO1B1^(*)5(521T>C)locus of SLCO1B1 gene were qualitatively detected by real-time fluorescence quantitative PCR method,which were compared with the reported data of hyperlipidemics from other regions in China,and the differences in genotype distribution among different regions were analyzed.【Results】The distribution frequency of ApoE genotype in dyslipidemia population was E2/E2(0.34%),E2/E3(14.00%),E3/E3(68.89%),E3/E4(13.22%),E2/E4(1.78%)and E4/E4(1.78%).SLCO1B1 genotype frequency:^(*)1a/^(*)1a(7.22%),^(*)1a/^(*)1b(32.89%),^(*)1b/^(*)1b(39.22%),^(*)1a/^(*)5(0.11%),^(*)1a/^(*)15(6.22%),^(*)1b/^(*)15(13.00%),^(*)15/^(*)15(1.33%).【Conclusion】E3/E3 genotype accounted for the largest proportion of ApoE in Xiaogan area,and^(*)1b/^(*)1b genotype in SLCO1B1 gene accounted for the highest proportion,that is,after the use of statins in hyperlipidemia population in Xiaogan area,most of them had a good effect and a low risk of myopathy.The E4 gene frequency distribution of ApoE genotype had statistical significance with blood lipid level(P<0.05).There was no significant difference between ApoE/SLCO1B1 and lipid levels(P>0.05).