Nitin Pothen1,2,3,4, Shveta Kansal1,2,3,4, Theodor Rais1,2,3,4, Stacy Doumas1,2,3,4, Ramon Solhkhah1,2,3,4. 1. Dr. Pothen and Dr. Kansal are with Ocean Medical Center, Hackensack Meridian Health in Brick, New Jersey. 2. Dr. Rias is with Firelands Regional Health System-Sandusky in Sandusky, Ohio, and Mercy Health-St. Vincent Medical Center in Toledo, Ohio. 3. Dr. Doumas is Psychiatry Residency Program Director at Jersey Shore University Medical Center in Neptune, New Jersey. 4. Dr. Solhkhah is Chairman of Department of Psychiatry at Jersey Shore University Medical Center in Neptune, New Jersey.
Abstract
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. Methods: 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. Results and Conclusions: 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.
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. Methods: 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. Results and Conclusions: 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.
Authors: S E Legge; M L Hamshere; S Ripke; A F Pardinas; J I Goldstein; E Rees; A L Richards; G Leonenko; L F Jorskog; K D Chambert; D A Collier; G Genovese; I Giegling; P Holmans; A Jonasdottir; G Kirov; S A McCarroll; J H MacCabe; K Mantripragada; J L Moran; B M Neale; H Stefansson; D Rujescu; M J Daly; P F Sullivan; M J Owen; M C O'Donovan; J T R Walters Journal: Mol Psychiatry Date: 2016-07-12 Impact factor: 15.992