Association of TNF-alpha gene with spontaneous deep intracerebral hemorrhage in the Taiwan population: a case control study.
BACKGROUND
Genetic factors may play a role in susceptibility to spontaneous deep intracerebral hemorrhage (SDICH). Previous studies have shown that TNF-alpha gene variation was associated with risks of subarachnoid hemorrhage in multiple ethnicities. The present case-control study tested the hypothesis that genetic variations of the TNF-alpha gene may affect the risk of Taiwanese SDICH. We examined the association of SDICH risks with four single nucleotide polymorphisms (SNPs) within the TNF-alpha gene promoter, namely T-1031C, C-863A, C-857T, and G-308A.


METHODS
Genotyping was determined by PCR-based restriction and electrophoresis assay for 260 SDICH patients and 368 controls. Associations were tested by logistic regression or general linear models with adjusting for multiple covariables in each gender group, and then in combined. Multiplicative terms of gender and each of the four SNPs were applied to detect the interaction effects on SDICH risks. To account for the multiple testing, permutation testing of 1,000 replicates was performed for empirical estimates.


RESULTS
In an additive model, SDICH risks were positively associated with the minor alleles -1031C and -308A in men (OR = 1.9, 95% CI 1.1 to 3.4, p = 0.03 and OR = 2.6, 95% CI 1.3 to 5.3, p = 0.005, respectively) but inversely associated with -863A in females (OR = 0.5, 95% CI 0.2 to 0.9, p = 0.03). There were significant interaction effects between gender and SNP on SDICH risks regarding SNPs T-1031C, C-863A, and G-308A (p = 0.005, 0.005, and 0.007, respectively). Hemorrhage size was inversely associated with -857T in males (p = 0.04).


CONCLUSIONS
In the Taiwan population, the associations of genetic variations in the TNF-alpha gene promoter with SDICH risks are gender-dependent.
Chen
Yi-Chun
YC
Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Taoyuan, Taiwan.
Hu
Fen-Ju
FJ
Chen
Phoebe
P
Wu
Yih-Ru
YR
Wu
Hsiu-Chuan
HC
Chen
Sien-Tsong
ST
Lee-Chen
Guey-Jen
GJ
Chen
Chiung-Mei
CM
D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D013624:Taiwan; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha