Exploration of MTDNA Variants In Relation To Post-traumatic Seizure After Severe Traumatic Brain Injury
Year: 2013
Type: article
Study design: Observational Study
Abstract: Post-traumatic seizures (PTS) are heterogeneous and their development has been proposed to depend on variation in the type and severity of injuries and differing genetic backgrounds of the patients. Identification of patients at risk for developing PTS has significant public health implications as those who suffer from PTS have limitations of daily living such as driving and may have increased caretaker burden and difficulty with reemployment. Genetic studies have revealed that several nuclear genetic variants may act as risk factors in the development of PTS. Many mitochondrial diseases due to variations in mitochondrial DNA (mtDNA) have seizure as part of their phenotype. However, no studies have yet focused on the role that mtDNA may play in the development of PTS. The goals of this study are to explore roles that mtDNA variants may play as independent risk factors for the development of both early (EPTS) and late (LPTS) post-traumatic seizures. To explore whether mtDNA variants act as effect modifiers of other injury related factors in relation to the development of EPTS/LPTS, and to explore if mtDNA variants effect the relationship between LPTS and GOS measures at 6 months post-injury. Nineteen mtDNA variants were genotyped in a population of 136 severe TBI patients. Additional genotypes were collected for 6 of the variants in the second stage of the analysis (n=332). No variant was significantly associated (at p<0.05) in the univariate analysis with EPTS or LPTS in either the smaller or larger subsets of the population. The A8701G variant showed the strongest association with EPTS in the univariate analysis (p=0.084) and was entered into a multivariate model. This model showed a significant effect for the variant (p=0.041). T16519C had the strongest univariate association with LPTS (p=0.053) and retained borderline significance when entered into a multivariate model (p=0.095). T16519C appeared to have the strongest trend towards a potential modifying effect with SDH and cranial surgery on the outcome of LPTS. T16519C and T195C may also have possible trends towards lower functional outcomes in those with LPTS. While no significant independent associations were found between the 19 mitochondrial variants and the outcome of PTS, the findings from this study may help guide future research in this area. This study was able to provide limited evidence that mitochondrial polymorphisms may in fact play a role in unraveling the complex phenotype of PTS.
Author: Jason Dechant
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W105306168