Polymorphism of tumor necrosis factor alpha (TNF-alpha) gene promoter, circulating TNF-alpha 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.


RESULTS
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.
Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, 1095# Jiefang Ave, Wuhan, 430030, China.
Guanglin
G
Cui
Haoran
H
Wang
Rui
R
Li
Lina
L
Zhang
Zongzhe
Z
Li
Yan
Y
Wang
Rutai
R
Hui
Hu
H
Ding
Dao Wen
DW
Wang
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016022:Case-Control Studies; D002461:Cell Line, Transformed; D015331:Cohort Studies; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D007511:Ischemia / Q000150:complications; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
D014409:Tumor Necrosis Factor-alpha