Polymorphism of tumor necrosis factor alpha (TNF-αlpha) gene promoter,circulating TNF-αlpha level,and cardiovascular risk factor for ischemic stroke

Background: tumor necrosis factor-α (tnf-α) is one of the most typical pro-inflammatory cytokines with both beneficial and destructive properties for the central nervous system. increasing evidences have demonstrated the important role of tnf-α in the development of ischemic stroke,but studies examining the possible association with stroke or direct functional effects of polymorphisms in tnf-α have been contradictory. findings: in this study,a 2-kb length of the proximal promoter of the tnf-α was screened and four polymorphisms were investigated in the case-control study. our data confirmed the association between -308g/a variant with stroke in 1,388 stroke patients and 1,027 controls and replicated in an independent population of 961 stroke patients and 821 controls (odds ratio (or) = 1.34,95% confidence interval (ci) =1.02 to 1.77 and or = 1.56,95% ci = 1.09 to 2.23,respectively). to reconcile the association between polymorphisms and stroke and to give a comprehensive picture of the genetic architecture of this important gene,we performed a meta-analysis of 15 published studies in an asian population. our results demonstrated an association between rs1800629 and ischemic stroke (or = 1.43,95% ci = 1.21 to 1.69). another meta-analysis results of 14 studies demonstrated that ischemic stroke patients have higher serum tnf-α level than the control subjects (standardized mean difference (smd) = 2.33,95% ci = 1.85 to 2.81). in vitro evaluation of potential interaction between variants of the tnf-α gene (-308g/a,-857c/t,and -1031t/c) demonstrated that these three polymorphisms could interact together to determine the overall activity of the tnf-α gene. conclusions: these findings strongly implicate the involvement of tnf-α in the pathogenesis of stroke. © 2012 cui et al.