Yang Hong-Wei, Xie Yanchen, Zhao Yuan, Sun Liang, Zhu Xiaoquan, Wang Shuhui, Zhang Yong-Qiang, Lei Ping, Meng Yunxiao
Geriatric Ward of Neurology, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, Tianjin Department of Neurology, Beijing Friendship Hospital, Capital Medical University The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
Medicine (Baltimore). 2017 May;96(20):e6798. doi: 10.1097/MD.0000000000006798.
In this study, we intended to genotype 2 single nucleotide polymorphisms (SNPs) of tumor necrosis factor α-induced protein 3 (TNFAIP3) genes and explore an association of TNFAIP3 genetic polymorphism with the patients of myasthenia gravis (MG) at clinical level. In brief, 215 of adult MG patients were divided into subgroups according to their clinical features, age of onset, thymic pathology, and autoantibodies. Two hundred thirty-five of healthy controls were also divided into subgroups with gender- and age-matched. The allele and genotype frequencies of subgrouped patients were found to be higher than those of healthy controls. The distribution of TNFAIP3 gene rs7749323A allele of late onset MG (LOMG, with positive acetylcholine receptor antibody and without thymoma) subgrouped patients was also significantly higher than that of gender- and age-matched healthy controls (7.4% vs 2.4%, odds ratio [OR] = 3.27, 95% confidence interval [CI] 1.01-10.6, P = .04). Furthermore, analysis to the genotype frequencies indicates that the carriers of rs7749323A allele of LOMG group became more frequent than that of age-matched healthy controls (14.9% vs 4.8%, OR = 3.47, 95% CI 1.04-11.6, dominant model: P = .03). It is interesting to notice that there is no significant association between the rs7749323 and susceptibility of other MG subgroups. Therefore, it is suggested that the SNPs in the 3' flanking region (rs7749323) of TNFAIP3 gene and the genetic variations of TNFAIP3 gene may take an important role in the susceptibility of LOMG.
在本研究中，我们旨在对肿瘤坏死因子α诱导蛋白3（TNFAIP3）基因的2个单核苷酸多态性（SNP）进行基因分型，并在临床水平上探讨TNFAIP3基因多态性与重症肌无力（MG）患者的相关性。简而言之，215例成年MG患者根据其临床特征、发病年龄、胸腺病理和自身抗体被分为亚组。235例健康对照也按性别和年龄匹配分为亚组。发现分组患者的等位基因和基因型频率高于健康对照。晚发型MG（LOMG，乙酰胆碱受体抗体阳性且无胸腺瘤）亚组患者的TNFAIP3基因rs7749323A等位基因分布也显著高于性别和年龄匹配的健康对照（7.4%对2.4%，优势比[OR]=3.27，95%置信区间[CI]1.01 - 10.6，P=0.04）。此外，对基因型频率的分析表明，LOMG组rs7749323A等位基因携带者比年龄匹配的健康对照更常见（14.9%对4.8%，OR=3.47，95%CI 1.04 - 11.6，显性模型：P=0.03）。有趣的是，rs7749323与其他MG亚组的易感性之间没有显著关联。因此，提示TNFAIP3基因3'侧翼区域的SNP（rs7749323）以及TNFAIP3基因的遗传变异可能在LOMG的易感性中起重要作用。
