中国汉族血脂异常成年人中SLCO1B1编码序列多态性与阿托伐他汀治疗前后血脂水平的关联
Associations Between the Polymorphisms in the Coding Sequence of SLCO1B1 and Blood Lipid Levels Before and After Treatment by Atorvastatin in the Chinese Han Adults with Dyslipidemia.
作者信息
Chen Chao, Tian Yan, Jia Fengshun, Feng Mingkun, Zhang Guoqiang, Li Qian, Zhang Yanwei, Sun Ningling, Hu Songnian, Ji Zheng
机构信息
Department of Cardiology, Tangshan Gongren Hospital, Tangshan, Hebei, People's Republic of China.
Beijing HuaGengYuan Pharmacogenomics Research Institute Co. Ltd., Beijing, People's Republic of China.
出版信息
Pharmgenomics Pers Med. 2024 Dec 20;17:551-561. doi: 10.2147/PGPM.S482289. eCollection 2024.
PURPOSE
Atorvastatin is commonly used to treat dyslipidemia; however, individual responses vary considerably. This study endeavors to evaluate the relationship between polymorphisms in the coding sequence (CDS) of SLCO1B1 gene and blood lipid levels before and after atorvastatin treatment among the Chinese Han adults with dyslipidemia.
PATIENTS AND METHODS
A total of 165 Chinese Han adults undergoing atorvastatin therapy were enrolled in this study and followed up quarterly. The complete CDS of the SLCO1B1 gene was sequenced to detect polymorphisms. Statistical analysis was utilized to assess the impacts of sex, age, body mass index (BMI), and polymorphisms on blood lipid levels before and after atorvastatin treatment.
RESULTS
Fourteen polymorphisms were identified in the SLCO1B1 CDS. Among them, four polymorphisms had mutant alleles present in over 20 patients. No polymorphism was found to correlate with blood lipid levels before treatment; in contrast, age, sex, and BMI did show correlations (<0.05). Notably, females had higher baseline blood lipid levels than males, indicating that sex had a more significant impact on baseline levels than age and BMI. The polymorphism rs2306283 was significantly correlated with the efficacy of atorvastatin (<0.05), whereas age, sex, and BMI were not. Carriers of the rs2306283 AA allele experienced a substantially greater reduction in total cholesterol (TC) and triglyceride (TG) levels after atorvastatin treatment. The other polymorphisms did not demonstrate any significant impact on atorvastatin's efficacy.
CONCLUSION
This study delved into the intricate genetic structure of polymorphisms in SLCO1B1 CDS and their roles in lipid metabolism and atorvastatin's efficacy among Chinese Han adults with dyslipidemia. The findings underscore the crucial role of the rs2306283 polymorphism in the response to atorvastatin's efficacy, highlighting the significance of pharmacogenomics in personalized medicine. It is thus advisable to consider genetic testing for SLCO1B1 variants to optimize atorvastatin therapy.
目的
阿托伐他汀常用于治疗血脂异常；然而，个体反应差异很大。本研究旨在评估中国汉族血脂异常成年人中，溶质载体有机阴离子转运体家族1成员B1（SLCO1B1）基因编码序列（CDS）多态性与阿托伐他汀治疗前后血脂水平之间的关系。
患者与方法
本研究共纳入165例接受阿托伐他汀治疗的中国汉族成年人，并每季度进行随访。对SLCO1B1基因的完整CDS进行测序以检测多态性。采用统计分析评估性别、年龄、体重指数（BMI）和多态性对阿托伐他汀治疗前后血脂水平的影响。
结果
在SLCO1B1 CDS中鉴定出14种多态性。其中，4种多态性的突变等位基因存在于20例以上患者中。未发现任何多态性与治疗前血脂水平相关；相比之下，年龄、性别和BMI确实显示出相关性（<0.05）。值得注意的是，女性的基线血脂水平高于男性，表明性别对基线水平的影响比年龄和BMI更显著。多态性rs2306283与阿托伐他汀的疗效显著相关（<0.05），而年龄、性别和BMI则不然。rs2306283 AA等位基因携带者在阿托伐他汀治疗后总胆固醇（TC）和甘油三酯（TG）水平的降低幅度明显更大。其他多态性对阿托伐他汀的疗效未显示出任何显著影响。
结论
本研究深入探讨了SLCO1B1 CDS多态性的复杂遗传结构及其在汉族血脂异常成年人脂质代谢和阿托伐他汀疗效中的作用。研究结果强调了rs2306283多态性在阿托伐他汀疗效反应中的关键作用，突出了药物基因组学在个性化医疗中的重要性。因此，建议考虑对SLCO1B1变体进行基因检测，以优化阿托伐他汀治疗。
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