Effect of SLCO1B1 T521C on Statin-Related Myotoxicity With Use of Lovastatin and Atorvastatin.
Effect of SLCO1B1 T521C on Statin-Related Myotoxicity With Use of Lovastatin and Atorvastatin.
复制标题
SLCO1B1 T521C对洛伐他汀和阿托伐他汀联合使用时他汀类药物相关肌毒性的影响。
DOI：
10.1002/cpt.2337
复制
发表时间：
2021-09
影响因子：
6.7
通讯作者：
Oni-Orisan A
中科院分区：
文献类型：
--
作者：
Lu B;Sun L;Seraydarian M;Hoffmann TJ;Medina MW;Risch N;Iribarren C;Krauss RM;Oni-Orisan A
SLCO 1B 1（rs 4149056）中的c.521 T>C变异等位基因与辛伐他汀诱导的肌毒性之间的关联在十多年前就被发现了;然而，这种关系是否代表了一种类效应仍然不完全清楚。本研究的目的是探讨rs 4149056基因型与服用阿托伐他汀和洛伐他汀的患者中他汀诱导的肌肉毒性的关系。研究参与者来自成人健康和老龄化遗传流行病学研究（GERA）队列。共有233例他汀类药物诱导的肌病+横纹肌溶解症病例符合入选标准，并与2，342例对照组相匹配。为了验证药物反应表型，我们复制了先前建立的rs 4149056基因型和辛伐他汀诱导的肌毒性之间的关联。特别是，与纯合子T等位基因携带者相比，C等位基因纯合子携带者发生辛伐他汀诱导的肌病+横纹肌溶解症的风险显著增加（CC vs TT，OR 4.6，95% CI 1.58-11.9，p= 2x 10 −3）。对于洛伐他汀使用者，C等位基因纯合子携带者发生他汀类药物诱导的肌病+横纹肌溶解症的风险也增加（CC vs TT，OR 4.5，95% CI 1.68-10.8，p= 1x 10 −3）。在阿托伐他汀使用者中，C等位基因纯合子携带者发生他汀类药物诱导的肌病的可能性是其两倍，尽管这种关联没有达到统计学显著性（CC vs TT，OR 2.0，95% CI 0.44-6.59，p=0.3）。总之，我们的研究结果表明rs 4149056与辛伐他汀相关的肌肉毒性的关联也可能扩展到洛伐他汀。需要更多的数据来确定阿托伐他汀使用者的相关程度。总而言之，这些数据扩展了基于药物遗传学的他汀类药物处方实践指南的证据基础。
The association between the c.521T>C variant allele in SLCO1B1 (rs4149056) and simvastatin-induced myotoxicity was discovered over a decade ago; however, whether this relationship represents a class effect is still not fully known. The aim of this study was to investigate the relationship between rs4149056 genotype and statin-induced myotoxicity in patients taking atorvastatin and lovastatin. Study participants were from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. A total of 233 statin-induced myopathy + rhabdomyolysis cases met the criteria for inclusion and were matched to 2,342 controls. To validate the drug response phenotype, we replicated the previously-established association between rs4149056 genotype and simvastatin-induced myotoxicity. In particular, compared to homozygous T allele carriers, there was a significantly increased risk of simvastatin-induced myopathy + rhabdomyolysis in homozygous carriers of the C allele (CC vs TT, OR 4.6, 95% CI 1.58-11.9, p=2x10−3). For lovastatin users, homozygous carriers of the C allele were also at increased risk of statin-induced myopathy + rhabdomyolysis (CC vs TT, OR 4.5, 95% CI 1.68-10.8, p=1x10−3). In atorvastatin users, homozygous carriers of the C allele were twice as likely to experience statin-induced myopathy, though this association did not achieve statistical significance (CC vs TT, OR 2.0, 95% CI 0.44-6.59, p=0.3). In summary, our findings suggest that the association of rs4149056 with simvastatin-related myotoxicity may also extend to lovastatin. More data is needed to determine the extent of the association in atorvastatin users. Altogether, these data expand the evidence-base for informing guidelines of pharmacogenetic-based statin prescribing practices.
登录
查看更多内容
影响因子：
6.7
作者：
Niemi, M.
通讯作者：
Niemi, M.
DOI：
10.1161/circgen.117.002043
发表时间：
2018-09
期刊：
Circulation. Genomic and precision medicine
影响因子：
--
作者：
Oni-Orisan A;Hoffmann TJ;Ranatunga D;Medina MW;Jorgenson E;Schaefer C;Krauss RM;Iribarren C;Risch N
通讯作者：
Risch N
影响因子：
4.8
作者：
Hsiang, BN;Zhu, YJ;Kirchgessner, TG
通讯作者：
Kirchgessner, TG
影响因子：
2
作者：
Gauderman, WJ
通讯作者：
Gauderman, WJ
影响因子：
2.8
作者：
Jacobson, TA
通讯作者：
Jacobson, TA