Association of promoter polymorphism -857C/T (rs1799724) in tumor necrosis factor gene with intracerebral hemorrhage in Korean males.
OBJECTIVE
Tumor necrosis factor (TNF) has been shown to be involved in the pathogenesis of hemorrhagic stroke, having deleterious effects on cerebral arteries by promoting inflammation and apoptosis in vascular and immune cells. In this study, we investigated genetic association between TNF gene and intracerebral hemorrhage (ICH) in a Korean population.


METHODS
Single nucleotide polymorphisms (SNPs) of TNF gene [-857C/T (rs1799724) and -308G/A (rs1800629)] were selected and genotyped using direct sequencing in 144 ICH patients and 455 control subjects. Genotype distribution and allele frequency were compared between cases and controls using logistic regression.


RESULTS
-857C/T was significantly associated with ICH in log-additive [odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.14-2.24, p = 0.0081], and recessive models (OR = 3.25, 95% CI = 1.28-8.27, p = 0.016). The frequency of the -857TT genotype increased in ICH patients. Allele frequency analysis also showed that the -857T allele was associated with an increased risk of ICH (OR = 1.62, 95% CI = 1.15-2.30, p = 0.006). In the analysis according to the gender, we found that the association of -857C/T was gender-different. The -857C/T was significantly associated with ICH only in males (OR = 1.99, 95% CI = 1.24-3.19, p = 0.0043 in males; OR = 1.30, 95% CI = 0.76-2.22, p = 0.34 in females).


CONCLUSIONS
These results suggest that promoter polymorphism of TNF gene, -857C/T, may be involved in the susceptibility of ICH in males.
a School of Medicine , Kohwang Medical Research Institute, Department of Pharmacology, Kyung Hee University , Seoul , Republic of Korea.
Hae Jeong
HJ
Park
a School of Medicine , Kohwang Medical Research Institute, Department of Pharmacology, Kyung Hee University , Seoul , Republic of Korea.
Su Kang
SK
Kim
b Department of Emergency Medicine , School of Medicine, Kyung Hee University , Seoul , Republic of Korea.
Hyun-Kyung
HK
Park
a School of Medicine , Kohwang Medical Research Institute, Department of Pharmacology, Kyung Hee University , Seoul , Republic of Korea.
Joo-Ho
JH
Chung
D000328:Adult; D000368:Aged; D002543:Cerebral Hemorrhage / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D056910:Republic of Korea; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha
Tumor necrosis factor; intracerebral hemorrhage; single nucleotide polymorphism