| Autor: |
Gracheva AS; The Department of Population Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia.; The Laboratory of Clinical Pathophysiology of Critical Conditions, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 107031 Moscow, Russia., Kashatnikova DA; The Laboratory of Ecological Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia.; The Laboratory of Molecular Pathophysiology, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia., Redkin IV; The Laboratory of Organoprotection in Critical Conditions, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 107031 Moscow, Russia., Zakharchenko VE; The Department of Clinical Laboratory Diagnostics, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 107031 Moscow, Russia., Kuzovlev AN; The Laboratory of Clinical Pathophysiology of Critical Conditions, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 107031 Moscow, Russia., Salnikova LE; The Laboratory of Clinical Pathophysiology of Critical Conditions, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 107031 Moscow, Russia.; The Laboratory of Ecological Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia.; The Laboratory of Molecular Immunology, National Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, Russia. |
| Abstrakt: |
Traumatic brain injury (TBI) is the leading cause of global mortality and morbidity. Because TBI is accident-related, the role of genetics in predisposing to TBI has been largely unexplored. However, the likelihood of injury may not be entirely random and may be associated with certain physical and mental characteristics. In this study, we analyzed the exomes of 50 patients undergoing rehabilitation after TBI. Patients were divided into three groups according to rehabilitation outcome: improvement, no change, and deterioration/death. We focused on rare, potentially functional missense and high-impact variants in genes intolerant to these variants. The concordant results from the three independent groups of patients allowed for the suggestion of the existence of a genetic predisposition to TBI, associated with rare functional variations in intolerant genes, with a prevalent dominant mode of inheritance and neurological manifestations in the genetic phenotypes according to the OMIM database. Forty-four of the 50 patients had one or more rare, potentially deleterious variants in one or more neurological genes. Comparison of these results with those of a 50-sampled matched non-TBI cohort revealed significant differences: P = 2.6 × 10 -3 , OR = 4.89 (1.77-13.47). There were no differences in the distribution of the genes of interest between the TBI patient groups. Our exploratory study provides new insights into the impact of genetics on TBI risk and is the first to address potential genetic susceptibility to TBI. |
