Association of TNF-alpha gene with spontaneous deep intracerebral hemorrhage in the Taiwan population: a case control study.

Association of TNF-alpha gene with spontaneous deep intracerebral hemorrhage in the Taiwan population: a case control study.
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DOI:
10.1186/1471-2377-10-41
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发表时间:
2010-06-10
期刊:
影响因子:
2.6
通讯作者:
Chen CM
Chen CM
中科院分区:
医学4区
文献类型:
--
作者:
Chen YC;Hu FJ;Chen P;Wu YR;Wu HC;Chen ST;Lee-Chen GJ;Chen CM

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遗传因素可能在自发性深部脑出血(SDICH)的易感性中起作用。既往研究表明,TNF-α基因变异与多种族蛛网膜下腔出血的风险相关。本病例对照研究验证了TNF-α基因的遗传变异可能影响台湾SDICH风险的假设。我们研究了SDICH风险与TNF-α基因启动子内的4个单核苷酸多态性(SNP)的相关性,即T-1031 C、C-863 A、C-857 T和G-308 A。采用PCR-限制性内切酶和电泳法对260例SDICH患者和368例对照者进行基因分型。通过逻辑回归或一般线性模型对每个性别组中的多个协变量进行调整,然后进行组合。应用性别和四个SNP中的每一个的乘法项来检测对SDICH风险的交互作用。为了解释多重检验,对1,000份重复样品进行排列检验以获得经验估计值。在加性模型中,SDICH风险与男性的次要等位基因-1031C和-308A呈正相关(OR = 1.9,95% CI 1.1至3.4,p = 0.03和OR = 2.6,95% CI 1.3至5.3,p = 0.005),但与女性中的-863A呈负相关(OR = 0.5,95% CI 0.2至0.9,p = 0.03)。性别和SNP对SNPs T-1031 C、C-863 A和G-308 A的SDICH风险有显著的交互作用(分别为p = 0.005、0.005和0.007)。男性出血量与-857 T呈负相关(p = 0.04)。在台湾人群中,TNF-α基因启动子的遗传变异与SDICH风险的相关性具有性别依赖性。
Genetic 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. 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. 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). In the Taiwan population, the associations of genetic variations in the TNF-α gene promoter with SDICH risks are gender-dependent.
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