Social, Economic and Administrative Pharmacy (SEAP) Graduate Program, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Pharmacogenomics J. 2021 Jun;21(3):296-307. doi: 10.1038/s41397-021-00208-w. Epub 2021 Feb 19.
This meta-analysis was conducted to determine the genotypic effects of rs4149056 and rs2306283 polymorphism in SLCO1B1 gene on myopathy in patients with statin. Studies were searched using multiple databases and selected following inclusion criteria. Two reviewers independently performed data extraction and assessments for risk of bias. Fixed-or-random-effect was applied to pool allele frequency/effects. Mixed-effect logit model was used to pool genotypic effects using individual patient data. Heterogeneity and publication bias were explored. Fourteen studies were pooled for rs4149056; the minor C allele frequency were 15% in Caucasians and 14% in Asians. Six studies were pooled for rs2306283; the minor G allele frequency was 34% in Caucasian and 75% in Asians. Genotypic effects of rs4149056 polymorphism in Caucasians indicated that statin users who carried CC and TC genotypes had a significantly higher risk of myopathy than those who carried TT genotype, with a pooled odds ratio (OR) of 2.9 (95% confidence interval, 1.59, 5.34) and 1.6 (1.20, 2.16), respectively. For subgroup analysis, CC and TC genotypes also suggested a higher risk of myopathy in simvastatin users [OR = 2.8 (1.17, 6.77) and OR = 1.8 (1.15, 2.77), respectively] and in atorvastatin users [OR = 4.0 (1.23, 12.63) and OR = 2.0 (1.11, 3.52), respectively] than those who carried TT genotype. There was no significant association between rs2306283 polymorphism and myopathy in Caucasians and Asians. There was no evidence of publication bias for both polymorphisms.
本荟萃分析旨在确定 SLCO1B1 基因中 rs4149056 和 rs2306283 多态性的基因型效应对他汀类药物引起的肌病的影响。使用多个数据库进行研究检索，并采用以下纳入标准进行选择。两位审阅者独立进行数据提取和偏倚风险评估。采用固定或随机效应模型对等位基因频率/效应进行合并。采用个体患者数据的混合效应逻辑模型对基因型效应进行合并。探索异质性和发表偏倚。rs4149056 纳入 14 项研究；白人中 minor C 等位基因频率为 15%，亚洲人为 14%。rs2306283 纳入 6 项研究；白人中 minor G 等位基因频率为 34%，亚洲人为 75%。白人中 rs4149056 多态性的基因型效应表明，携带 CC 和 TC 基因型的他汀类药物使用者发生肌病的风险显著高于 TT 基因型携带者，合并优势比（OR）分别为 2.9（95%置信区间，1.59-5.34）和 1.6（1.20-2.16）。亚组分析显示，辛伐他汀使用者中 CC 和 TC 基因型也提示肌病风险升高[OR = 2.8（1.17-6.77）和 OR = 1.8（1.15-2.77）]，阿托伐他汀使用者中 CC 和 TC 基因型也提示肌病风险升高[OR = 4.0（1.23-12.63）和 OR = 2.0（1.11-3.52）]，均高于 TT 基因型携带者。rs2306283 多态性与白人和亚洲人肌病之间无显著关联。两种多态性均未发现发表偏倚的证据。
