Cytokine Gene Polymorphisms and Outcome after Traumatic Brain Injury

Abstract

Clinical outcome after traumatic brain injury (TBI) is variable and cannot easily be predicted. There is increasing evidence to suggest that there may be genetic influences on outcome. Cytokines play an important role in mediating the inflammatory response provoked within the central nervous system after TBI. This study was designed to identify associations between cytokine gene polymorphisms and clinical outcome 6 months after head injury. A prospectively identified cohort of patients (n = 1096, age range 0-93 years, mean age 37) was used. Clinical outcome at 6 months was assessed using the Glasgow Outcome Scale. In an initial screen of 11 cytokine gene single nucleotide polymorphisms (SNPs) previously associated with disease susceptibility or outcome (TNFA -238 and -308, IL6 -174, -572 and -597, IL1A -889, IL1B -31, -511 and + 3953, and TGFB -509 and -800), TNFA -308 was identified as having a likely association. The TNFA -308 SNP was further evaluated, and a significant association was identified, with 39% of allele 2 carriers having an unfavorable outcome compared with 31% of non-carriers (adjusted odds ratio 1.67, confidence interval 1.19-2.35, p = 0.003). These findings are consistent with experimental and clinical data suggesting that neuroinflammation has an impact on clinical outcome after TBI and that tumor necrosis factor alpha plays an important role in this process.

COMTVal158Metand Cognitive and Functional Outcomes after Traumatic Brain Injury

“…1 Thus, examination of just one of these alleles in isolation (candidate gene approach) does not allow for any underlying relationships between SNPs and genes to be studied and does not take into account environmental modifications of gene expression. 2 A number of recent reviews 6,65 and studies investigating influence of other polymorphisms on outcome after TBI 66 have advocated for the examination of the interactions between a range of candidate alleles likely to contribute to cognition. Full screening of the COMT gene and other dopaminergic genes, such as dopamine receptor D2 gene or ankyrin repeat and kinase domain-containing 1, which are known to be associated with cognition, is recommended.…”

A Longitudinal Diffusion Tensor Imaging Study Assessing White Matter Fiber Tracts after Sports-Related Concussion

“…32,87 Further, variability in the trajectories of the diffusion measures might be affected by differences in number of previous concussions, 68 timing of each athlete's return to play (see Table 1), and individual genetic predisposition. 88,89 Experimental designs of future studies should include the assessment of subconcussive hits, extending at least to the end of season.…”

Roles of Pro- and Anti-inflammatory Cytokines in Traumatic Brain Injury and Acute Ischemic Stroke

“…A meta-analysis on AIS risk in individuals with TNF-α-308G/A gene versus-238G/A gene polymorphisms, both of which lead to high TNF-α production, suggests diferences in AIS risk associated with these SNPs in Caucasians versus Asians; the TNF-α-308G/A gene polymorphism was protective in Asians, while the TNF-α-238G/A gene polymorphism was associated with a higher risk of AIS in Caucasians [92]. In a study of the TNF-α-308G/A gene polymorphism in TBI patients, those with this polymorphism had worse clinical outcomes as measured by the Glasgow outcome scale at 6 months post-injury [93].…”

“…In both AIS and TBI, single-nucleotide polymorphisms (SNPs) in TNF-α have been correlated to diferent risk proiles for disease severity [91][92][93]. A meta-analysis on AIS risk in individuals with TNF-α-308G/A gene versus-238G/A gene polymorphisms, both of which lead to high TNF-α production, suggests diferences in AIS risk associated with these SNPs in Caucasians versus Asians; the TNF-α-308G/A gene polymorphism was protective in Asians, while the TNF-α-238G/A gene polymorphism was associated with a higher risk of AIS in Caucasians [92].…”