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.