The role of vitamin D and SLCO1B1*5 gene polymorphism in statin-associated myalgias
The role of vitamin D and SLCO1B1*5 gene polymorphism in statin-associated myalgias
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DOI：
10.4161/derm.2.2.13509
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发表时间：
2010-01-01
期刊：
影响因子：
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通讯作者：
Feldman, David
中科院分区：
文献类型：
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作者：
Linde, Randy;Peng, Lihong;Feldman, David
肌痛是他汀类药物最常见的副作用，也是导致停止治疗的最常见原因。维生素D在肌肉中具有已知的生理功能，维生素D缺乏会导致肌痛，纠正维生素D会导致肌肉症状的消失。521T>；C SLCO1B1*5基因的多态与他汀类药物摄取有关的肝脏阴离子转运蛋白编码基因的功能降低被发现可以解释大多数他汀类药物相关的肌肉症状。据报道，与他汀类药物相关的肌痛患者服用维生素D后会有所改善。因此，我们调查了(I)肌痛缺乏患者补充维生素D是否会导致对随后的他汀类药物治疗的耐受性，以及(Ii)维生素D状态是否会改变SLCO1B1*5基因对肌痛风险的影响。通过对接受他汀类药物治疗期间因任何原因测定25-羟基维生素D[25(OH)D]的患者(包括46名同意接受基因分型的患者)的回顾性队列研究，我们发现了强有力的证据表明，维生素D缺乏的患者补充维生素D可以改善肌痛。在21名维生素D缺乏、不能耐受他汀类药物相关性肌痛的患者中，15名再次服用他汀类药物的患者中有14名随后无症状，1名患者出现轻微和可耐受的症状，远远超过未经治疗的获得性耐受率(p=0.01)。此外，虽然SLCO1B1*5基因与肌痛风险增加三倍相关(p=0.07)，但这种风险与维生素D状态无关(p=0.60)。
Myalgias are the most common side effect of statin use and the commonest cause for discontinuing therapy. Vitamin D has known physiologic functions in muscle and vitamin D deficiency is known to cause myalgias, with its correction leading to disappearance of muscle symptoms. The 521T>C SLCO1B1*5 gene polymorphism decreasing function in the gene coding for a liver anion transporter that is responsible for statin uptake has been found to explain the majority of statin-associated muscle symptoms. Patients with statin-associated myalgias have been reported to improve with vitamin D supplementation. We therefore investigated (i) whether repletion of vitamin D in deficient patients with myalgias could lead to tolerance for subsequent statin therapy and (ii) whether vitamin D status modifies the effect of the SLCO1B1*5 genotype on myalgia risk. Using a retrospective cohort of 64 patients in whom 25-hydroxyvitamin D [25(OH) D] had been measured for any reason while on statin therapy, including 46 patients who consented to be genotyped, we found strong evidence showing that repletion of vitamin D in vitamin D deficient patients improved myalgias. Of 21 vitamin D deficient patients with intolerable statin-associated myalgias, 14 of 15 rechallenged with statins were subsequently symptomfree, with one patient experiencing mild and tolerable symptoms, far exceeding expected rates of acquired tolerability with no therapy (p = 0.01). In addition, while the SLCO1B1*5 genotype was associated with a three-fold increased risk of myalgias (p = 0.07), this risk was not found to differ by vitamin D status (p = 0.60).