三磷酸腺苷结合盒转运体A1基因多态性与辛伐他汀调脂的关系

目的：研究三磷酸腺苷结合盒转运体A1（ABCA1）基因R219K多态性对血脂水平及辛伐他汀调脂治疗的影响。方法：原发性高脂血症患者80例，给予辛伐他汀20mg／d，治疗8周，治疗前后测定患者血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）及高密度脂蛋白胆固醇（HDL-C）浓度，治疗期间进行不良反应的监测。使用TaqMan荧光探针技术测定患者ABCA1基因R219K多态性。根据不同的基因型分组，比较不同基因型之间血脂水平变化的差异。进而判定不同基因型对血脂水平及辛伐他汀疗效的影响。结果：ABCA1 R219K基因存在三种基因型，即RR、RK和KK基因型。辛伐他汀治疗前RR基因型和RK基因型HDL—C水平明显低于KK基因型（P〈0．05）。辛伐他汀治疗8周后，三种基因型TC、TG、LDL-C水平均较前降低，HDL—C水平均较前升高；治疗后RR及RK基因型HDL—C水平仍低于KK型（P〈O．05）；但TC、TG、LDL—C和HDL—C水平的变化在不同基因型组之间无显著差异（P〉0．05）。结论：ABCA1基因R219K单核苷酸多态性可影响HDL—C水平，K等位基因与高HDL-C水平相关，但与辛伐他汀治疗的个体差异性无关。

Association of ABCA1 R219K polymorphism with therapeutic effects of simvastatin

Objective： To investigate the interactions between R219K polymorphisms in ATP-binging cassette （ABC） A1 gene and the plasma lipid levels, and to compared therapeutic effect of simvastatin in different genotypes. Methods; Eighty hypercholesterolemic patients were included in this study. Subjects entering the study were treated with 20 mg/ d simvastatin for 8 weeks. Levels of serum total cholesterol （TC）, triglyceride （TG）, low--density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） were measured before treatment and after 8 weeks of treatment. ABCA1 gene polymorphism in patients was detected by TaqMan technology. Results： Three genotypes were detected in R219K single nucleotide polymorphism of ABCA1 gene in our study. There were significant differences among ABCA1 R219K genotypes in HDL-C levels before therapy （P〈0.05）. The individuals with the RR/RK genotypes had a lower HDL-C level than that of the KK genotype （P〈0. 05）. After treatment of simvastatin for 8 weeks, all the levels of TC, TG and LDL-C decreased and the value of HDL-C increased than before treatment. The RR/RK genotypes still had a lower HDL-C level than KK genotype （P〈0.05）, but no significant differences was found about the change of TC, TG, LDL-C and HDL-C levels in different genotypes to simvastatin （ P〉0.05）. Conclusion： ABCA1 R219K single nucleotide polymorphisms significantly influences the plasma levels of HDL-C, KK gene may be associated with higher HDL-C level. No association was found between different genotypes and the change of plasma lipids levels.