当前位置: X-MOL 学术Eur. Heart J. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A common missense variant of LILRB5 is associated with statin intolerance and myalgia
European Heart Journal ( IF 39.3 ) Pub Date : 2017-08-29 , DOI: 10.1093/eurheartj/ehx467
Moneeza K Siddiqui 1 , Cyrielle Maroteau 1 , Abirami Veluchamy 1 , Aleksi Tornio 1 , Roger Tavendale 1 , Fiona Carr 1 , Ngu-Uma Abelega 1 , Dan Carr 2 , Katyrzyna Bloch 2 , Par Hallberg 3 , Qun-Ying Yue 4 , Ewan R Pearson 1 , Helen M Colhoun 1, 5 , Andrew D Morris 1, 6 , Eleanor Dow 7 , Jacob George 7 , Munir Pirmohamed 2 , Paul M Ridker 8 , Alex S F Doney 7 , Ana Alfirevic 2 , Mia Wadelius 3 , Anke-Hilse Maitland-van der Zee 9, 10 , Daniel I Chasman 8 , Colin N A Palmer 1 ,
Affiliation  

Abstract Aims A genetic variant in LILRB5 (leukocyte immunoglobulin-like receptor subfamily-B) (rs12975366: T > C: Asp247Gly) has been reported to be associated with lower creatine phosphokinase (CK) and lactate dehydrogenase (LDH) levels. Both biomarkers are released from injured muscle tissue, making this variant a potential candidate for susceptibility to muscle-related symptoms. We examined the association of this variant with statin intolerance ascertained from electronic medical records in the GoDARTS study. Methods and results In the GoDARTS cohort, the LILRB5 Asp247 variant was associated with statin intolerance (SI) phenotypes; one defined as having raised CK and being non-adherent to therapy [odds ratio (OR) 1.81; 95% confidence interval (CI): 1.34–2.45] and the other as being intolerant to the lowest approved dose of a statin before being switched to two or more other statins (OR 1.36; 95% CI: 1.07–1.73). Those homozygous for Asp247 had increased odds of developing both definitions of intolerance. Importantly the second definition did not rely on CK elevations. These results were replicated in adjudicated cases of statin-induced myopathy in the PREDICTION-ADR consortium (OR1.48; 95% CI: 1.05–2.10) and for the development of myalgia in the JUPITER randomized clinical trial of rosuvastatin (OR1.35, 95% CI: 1.10–1.68). A meta-analysis across the studies showed a consistent association between Asp247Gly and outcomes associated with SI (OR1.34; 95% CI: 1.16–1.54). Conclusion This study presents a novel immunogenetic factor associated with statin intolerance, an important risk factor for cardiovascular outcomes. The results suggest that true statin-induced myalgia and non-specific myalgia are distinct, with a potential role for the immune system in their development. We identify a genetic group that is more likely to be intolerant to their statins.

中文翻译:

LILRB5 的常见错义变体与他汀类药物不耐受和肌痛有关

摘要目的 LILRB5(白细胞免疫球蛋白样受体亚家族-B)(rs12975366:T > C:Asp247Gly)中的一个遗传变异与较低的肌酸磷酸激酶(CK)和乳酸脱氢酶(LDH)水平有关。这两种生物标志物都是从受伤的肌肉组织中释放出来的,这使得这种变体成为对肌肉相关症状易感性的潜在候选者。我们检查了 GoDARTS 研究中从电子病历中确定的这种变体与他汀类药物不耐受的关系。方法和结果 在 GoDARTS 队列中,LILRB5 Asp247 变体与他汀类药物不耐受 (SI) 表型相关;一种定义为 CK 升高且不依从治疗 [优势比 (OR) 1.81;95% 置信区间 (CI):1.34–2。45] 和另一个在转换为两种或多种其他他汀类药物之前对最低批准剂量的他汀类药物不耐受(OR 1.36;95% CI:1.07-1.73)。Asp247 的纯合子增加了发展这两种不耐受定义的几率。重要的是,第二个定义不依赖于 CK 升高。这些结果在 PREDICTION-ADR 联盟 (OR1.48; 95% CI: 1.05–2.10) 和 JUPITER 瑞舒伐他汀随机临床试验 (OR1.35, 95% CI:1.10–1.68)。一项跨研究的荟萃分析显示,Asp247Gly 与 SI 相关结果之间存在一致的关联(OR1.34;95% CI:1.16-1.54)。结论 本研究提出了一种与他汀类药物不耐受相关的新型免疫遗传因子,心血管结局的一个重要危险因素。结果表明,真正的他汀类药物诱导的肌痛和非特异性肌痛是不同的,免疫系统在它们的发育中具有潜在的作用。我们确定了一个更可能对其他汀类药物不耐受的基因组。
更新日期:2017-08-29
down
wechat
bug