Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Am Heart J. 2013 Jun;165(6):1008-14. doi: 10.1016/j.ahj.2013.01.025. Epub 2013 Apr 10.
Carriers of the rs4363657C and rs4149056C alleles in SLCO1B1 have increased myopathic complaints when taking simvastatin. Whether rosuvastatin has a similar effect is uncertain. This study assesses whether SLCO1B1 polymorphisms relate to clinical myalgia after rosuvastatin therapy.
In the JUPITER trial, participants without prior cardiovascular disease or diabetes who had low-density lipoprotein cholesterol <130 mg/dL and C-reactive protein ≥2 mg/L were randomly allocated to rosuvastatin 20 mg or placebo and followed for the first cardiovascular disease events and adverse effects. We evaluated the effect of rs4363657 and rs4149056 in SLCO1B1, which encodes organic anion-transporting polypeptide OATP1B1, a regulator of hepatic statin uptake, on clinically reported myalgia.
Among 4,404 participants allocated to rosuvastatin, clinical myalgia occurred with a rate of 4.1 events per 100 person-years as compared with 3.7 events per 100 person-years among 4,378 participants allocated to placebo (hazard ratio [HR] 1.13, 95% CI 0.98-1.30). Among those on rosuvastatin, there were no differences in the rate of myalgia among those with the rs4363657C (HR 0.95, 95% CI 0.79-1.14 per allele) or the rs4149056C allele (HR 0.95, 95% CI 0.79-1.15 per allele) compared with those without the C allele. Similar null data were observed when the myalgia definition was broadened to include muscle weakness, stiffness, or pain. None of the 3 participants on rosuvastatin or the 3 participants on placebo with frank myopathy had the minor allele at either polymorphism.
There appears to be no increased risk of myalgia among users of rosuvastatin who carry the rs4363657C or the rs4149056C allele in SLCO1B1.
携带 SLCO1B1 基因中的 rs4363657C 和 rs4149056C 等位基因的患者在服用辛伐他汀时会出现更多的肌肉疾病症状。而瑞舒伐他汀是否有类似的影响尚不确定。本研究旨在评估 SLCO1B1 多态性与瑞舒伐他汀治疗后临床肌肉痛之间的关系。
在 JUPITER 试验中，参与者无心血管疾病或糖尿病史，低密度脂蛋白胆固醇<130mg/dL，C 反应蛋白≥2mg/L，随机分配至瑞舒伐他汀 20mg 或安慰剂组，并随访首次心血管疾病事件和不良反应。我们评估了 SLCO1B1 中的 rs4363657 和 rs4149056 对临床报告的肌肉痛的影响，SLCO1B1 编码有机阴离子转运多肽 OATP1B1，是调节肝脏他汀类药物摄取的蛋白。
在 4404 名接受瑞舒伐他汀治疗的参与者中，临床肌肉痛的发生率为每 100 人年 4.1 例，而在 4378 名接受安慰剂治疗的参与者中，发生率为每 100 人年 3.7 例（风险比 [HR]1.13，95%置信区间 [CI]0.98-1.30）。在接受瑞舒伐他汀治疗的患者中，rs4363657C 等位基因（每等位基因 HR0.95，95%CI0.79-1.14）或 rs4149056C 等位基因（每等位基因 HR0.95，95%CI0.79-1.15）携带者的肌肉痛发生率与无 C 等位基因携带者之间无差异。当肌肉痛定义放宽为包括肌肉无力、僵硬或疼痛时，也观察到了类似的无效数据。在接受瑞舒伐他汀治疗的 3 名患者或接受安慰剂治疗的 3 名患者中，均未发现这两种多态性的次要等位基因。
在携带 SLCO1B1 基因中的 rs4363657C 或 rs4149056C 等位基因的瑞舒伐他汀使用者中，肌肉痛的风险似乎没有增加。
