Park Hae Jeong, Kim Su Kang, Park Hyun-Kyung, Chung Joo-Ho
a School of Medicine , Kohwang Medical Research Institute, Department of Pharmacology, Kyung Hee University , Seoul , Republic of Korea.
b Department of Emergency Medicine , School of Medicine, Kyung Hee University , Seoul , Republic of Korea.
Neurol Res. 2017 Jan;39(1):90-95. doi: 10.1080/01616412.2016.1251696. Epub 2016 Nov 4.
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.
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.
-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).
These results suggest that promoter polymorphism of TNF gene, -857C/T, may be involved in the susceptibility of ICH in males.
肿瘤坏死因子（TNF）已被证明参与出血性中风的发病机制，通过促进血管和免疫细胞的炎症和凋亡，对脑动脉产生有害影响。在本研究中，我们调查了韩国人群中TNF基因与脑出血（ICH）之间的遗传关联。
选择TNF基因的单核苷酸多态性（SNP）[-857C/T（rs1799724）和-308G/A（rs1800629）]，并采用直接测序法对144例ICH患者和455例对照者进行基因分型。使用逻辑回归比较病例组和对照组之间的基因型分布和等位基因频率。
-857C/T在对数相加模型[比值比（OR）=1.60，95%置信区间（CI）=1.14-2.24，p=0.0081]和隐性模型（OR=3.25，95%CI=1.28-8.27，p=0.016）中与ICH显著相关。-857TT基因型在ICH患者中的频率增加。等位基因频率分析还表明，-857T等位基因与ICH风险增加相关（OR=1.62，95%CI=1.15-2.30，p=0.006）。在按性别进行的分析中，我们发现-857C/T的关联存在性别差异。-857C/T仅在男性中与ICH显著相关（男性中OR=1.99，95%CI=1.24-3.19，p=0.0043；女性中OR=1.30，95%CI=0.76-2.22，p=0.34）。
这些结果表明，TNF基因启动子多态性-857C/T可能与男性ICH易感性有关。
