A common missense variant of LILRB5 is associated with statin intolerance and myalgia.
A common missense variant of LILRB5 is associated with statin intolerance and myalgia.
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DOI：
10.1093/eurheartj/ehx467
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发表时间：
2017-12-21
影响因子：
39.3
通讯作者：
PREDICTION-ADR Consortium
中科院分区：
文献类型：
--
作者：
K Siddiqui M;Maroteau C;Veluchamy A;Tornio A;Tavendale R;Carr F;Abelega NU;Carr D;Bloch K;Hallberg P;Yue QY;Pearson ER;Colhoun HM;Morris AD;Dow E;George J;Pirmohamed M;Ridker PM;Doney ASF;Alfirevic A;Wadelius M;Maitland-van der Zee AH;Chasman DI;Palmer CNA;PREDICTION-ADR Consortium
LILRB5(白细胞免疫球蛋白样受体B亚家族)(rs12975366：T >； C：Asp247Gly)的一个基因变异被报道与较低的肌酸磷酸酶(CK)和乳酸脱氢酶(LDH)水平有关。这两种生物标记物都是从受损的肌肉组织中释放出来的，这使得该变体成为肌肉相关症状易感性的潜在候选者。在GoDARTS研究中，我们检查了这种变异与他汀类药物不耐受之间的关系，这是从GoDARTS研究的电子病历中确定的。在GoDARTS队列中，LILRB5 Asp247变异与他汀类药物不耐受(SI)表型有关；一种被定义为CK升高并未坚持治疗[优势比(OR)1.81；95%可信区间(CI)：1.34-2.45]，另一种被定义为在转换为两种或更多其他他汀类药物之前对批准的最低剂量的他汀类药物不耐受(OR 1.36；95%CI：1.07-1.73)。那些Asp247纯合子的人患上这两种不耐受定义的几率都增加了。重要的是，第二个定义不依赖于CK高程。这些结果在Forecast-ADR联合体(OR1.48；95%CI：1.05-2.10)和Jupiter随机临床试验中的肌痛发展(OR1.35，95%CI：1.10-1.68)的他汀类诱导性肌病的判定病例中得到了重复。所有研究的荟萃分析显示，Asp247Gly与SI相关的结果一致相关(OR1.34；95%CI：1.16-1.54)。这项研究提出了一种与他汀类药物不耐受相关的新的免疫遗传因素，这是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展中具有潜在的作用。我们确定了一个更有可能对他汀类药物不耐受的基因群体。
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. 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). 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.
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影响因子：
4.1
作者：
Rodríguez-Perea AL;Montoya CJ;Olek S;Chougnet CA;Velilla PA
通讯作者：
Velilla PA
影响因子：
2.9
作者：
Amend, Kandace L.;Landon, Joan;McAfee, Andrew
通讯作者：
McAfee, Andrew
影响因子：
5.3
作者：
LANSBERG, PJ;MITCHEL, YB;HAYDEN, MR
通讯作者：
HAYDEN, MR
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
32.4
作者：
Kuswanto W;Burzyn D;Panduro M;Wang KK;Jang YC;Wagers AJ;Benoist C;Mathis D
通讯作者：
Mathis D