目的:探讨新乡地区人群ABCB1(2677T>G)和SLCO1B1(521T>C)单核苷酸多态性(SNPs)对心脑血管疾病患者服用阿托伐他汀的不良反应及降脂疗效的影响。方法:通过荧光原位杂交法、高效液相色谱法等,考察患者SLCO1B1(521T>C)、ABCB1(2677T>G)SNPs与阿托伐他汀药动学、药效学及不良反应的相关性。结果:在新乡市中心医院的90例入选患者中,SLCO1B1(521T>C)、ABCB1(2677T>G)等位基因突变频率分别为18.1%和69.8%。用药前后,SLCO1B1(521T>C)SNPs与阿托伐他汀的血药浓度有相关性,但对其疗效及肌痛风险影响较小,各基因型间差异无显著性。ABCB1(2677T>G)各基因型患者阿托伐他汀血药浓度组内差异具有显著性(P<0.05),相比ABCB1 2677T等位基因,携带ABCB1 2677G基因的患者对LDL-C降低作用更强,且出现肝毒性的风险较高。结论:ABCB1(2677T>G)SNPs与阿托伐他汀的降脂疗效及肝毒性具有相关性,G等位基因可能是阿托伐他汀致肝毒性的因素之一。SLCO1B1(521T>C)SNPs对阿托伐他汀的降脂疗效及肌痛风险无显著影响。
OBJECTIVE To investigate the adverse reaction and lipid-regulating efficacy of atorvastatin (ATV) in patients with cardiovascular disease through the single nucleotide polymorphisms (SNPs) of SLCO1B1 (521T>C) and ABCB1 (2677T>G) in Xinxiang.METHODS Fluorescence in situ hybridization (FISH) for the gene polymorphisms, HPLC for the blood concentration of ATV were carried out for these patients to analyze the relationship between the PK/PD, the adverse of drug reactions (ADRs) of ATV and SLCO1B1 (521T>C), ABCB1 (2677T>G) SNPs.RESULTS The mutation frequencies of SLCO1B1 (521T>C) and ABCB1 (2677T>G) were 18.1% and 69.8%, respectively. The SLCO1B1 (521T>C) SNPs and plasma concentration were significantly correlated before and after treatment, while there was no statistical significance in the relationship of the lipid-lowing therapy and myopathy with SLCO1B1 (521T>C) SNPs. However, the plasma concentration of ATV among the three genotype groups of ABCB1 (2677T>G) showed significant difference. Compared with the patients carrying the allele ABCB1 2677T, patients with the allele ABCB1 2677G showed significantly greater LDL-C reduction in response to ATV therapy and there was a higher risk of hepatotoxicity in the therapy of ATV.CONCLUSION The ABCB1 (2677T>G) SNPs is associated with the lipid-lowing therapy and atorvastatin-induced liver injury (AILI), G allele gene may be the susceptible gene of AILI. No significant impact of SLCO1B1 (521T>C) SNPs on the lipid-lowering efficacy and myopathy of ATV has been found.
Chinese Journal of Hospital Pharmacy