Abstract
BackgroundGenetic factors may play a role in susceptibility to spontaneous deep intracerebral hemorrhage (SDICH). Previous studies have shown that TNF-α 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-α gene may affect the risk of Taiwanese SDICH. We examined the association of SDICH risks with four single nucleotide polymorphisms (SNPs) within the TNF-α gene promoter, namely T-1031C, C-863A, C-857T, and G-308A.MethodsGenotyping 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.ResultsIn 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).ConclusionsIn the Taiwan population, the associations of genetic variations in the TNF-α gene promoter with SDICH risks are gender-dependent.
Highlights
Genetic factors may play a role in susceptibility to spontaneous deep intracerebral hemorrhage (SDICH)
We have shown sex differences in the etiological spectrum of SDICH in the young, in which cryptogenic etiology and underlying vascular anomaly are significantly higher in females while hypertension attributes to a higher SDICH risk in males [6]
The purpose of this study is to evaluate whether any particular polymorphism of Tumor necrosis factor α (TNF-α) gene would predispose to SDICH and modify the 30-day outcome of SDICH events in the Taiwan population
Summary
Genetic factors may play a role in susceptibility to spontaneous deep intracerebral hemorrhage (SDICH). The present case-control study tested the hypothesis that genetic variations of the TNF-α gene may affect the risk of Taiwanese SDICH. Candidate genes reported as associated with SICH were involved in the pathways of the vessel wall integrity (ACE, APOE, neprilysin, endoglin, TGF-β1), endothelial dysfunction (ACE), inflammation markers (IL-6, TNF), and hemostasis (APOE, CD-14, Factor VII and XIII, VKORC1). These studies were mainly conducted in lobar SICH. The number of genetic studies of SDICH is limited [2,8,9,10]
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