Pothen Nitin, Kansal Shveta, Rais Theodor, Doumas Stacy, Solhkhah Ramon
Dr. Pothen and Dr. Kansal are with Ocean Medical Center, Hackensack Meridian Health in Brick, New Jersey.
Dr. Rias is with Firelands Regional Health System-Sandusky in Sandusky, Ohio, and Mercy Health-St. Vincent Medical Center in Toledo, Ohio.
Innov Clin Neurosci. 2019 Nov 1;16(11-12):28-31.
Clozapine-induced agranulocytosis, malignant hyperthermia (MH), statin-induced myopathy, and neuroleptic malignant syndrome (NMS) are all serious drug reactions with significant overlap in terms of clinical symptomatology. The use of clozapine can lead to neutropenia, as well as the development of NMS; thus, it seemed logical to explore a possible common genetic background for the development of these two adverse effects. Furthermore, due to the overwhelming clinical resemblance between NMS, MH, and statin-induced myopathy, we decided specifically to search for a common genetic background in the development of these conditions. We searched the PubMed, OMIM, WikiGenes, Medline, and Google Scholar databases to identify articles pertinent to our subject published over the last 30 years. Articles were reviewed according to our inclusion/exclusion criteria, and irrelevant articles were excluded. In our exploration for a common genetic background between clozapine-induced agranulocytosis, MH, NMS, and statin-induced myopathy, we identified the SLCO1B1 gene, which was common to three of these four conditions (MH, statin-induced myopathy, and clozapine-induced agranulocytosis). Although we did not find a gene common among NMS and the other conditions, the overlap of clinical symptoms between NMS, MH, and statin-induced myopathy did not allow us to rule out the possibility of a common factor, in terms of genetic predisposition, between these conditions. Future studies can aid to fill in the gaps of knowledge in terms of any genetic linkage between these three conditions and the mechanism of their associations.
氯氮平所致粒细胞缺乏症、恶性高热（MH）、他汀类药物所致肌病以及抗精神病药恶性综合征（NMS）均为严重的药物不良反应，在临床症状学方面有显著重叠。使用氯氮平可导致中性粒细胞减少以及NMS的发生；因此，探索这两种不良反应发生的可能共同遗传背景似乎是合乎逻辑的。此外，由于NMS、MH和他汀类药物所致肌病在临床上极为相似，我们特意决定寻找这些病症发生的共同遗传背景。我们检索了PubMed、OMIM、WikiGenes、Medline和谷歌学术数据库，以确定过去30年发表的与我们主题相关的文章。根据我们的纳入/排除标准对文章进行了审查，排除了无关文章。在探索氯氮平所致粒细胞缺乏症、MH、NMS和他汀类药物所致肌病之间的共同遗传背景时，我们发现了SLCO1B1基因，这是这四种病症中的三种（MH、他汀类药物所致肌病和氯氮平所致粒细胞缺乏症）所共有的。虽然我们没有发现NMS与其他病症共有的基因，但NMS、MH和他汀类药物所致肌病之间临床症状的重叠使我们无法排除在遗传易感性方面这些病症之间存在共同因素的可能性。未来的研究有助于填补这三种病症之间任何遗传联系及其关联机制方面的知识空白。
