变种TNFSF15预测了中国克罗恩病患者的疾病进展
Qi Zhang1,2,3,4, Wei Wang1,2,3,4, Bingjie Xiang1,2,3,4
1Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.
TNFSF15基因变体rs6478109与克罗恩病 (CD) 和严格治疗有关. 在中国的CD患者中,GG基因型可以预测疾病进展和纤维化相关蛋白质表达的增加.
科学领域:
- 遗传学 遗传学 是一个
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
背景情况:
- 瘤坏死因子超级家族成员15 (TNFSF15) 基因变异与克罗恩病 (CD),肠道纤维化和硬化有关.
- 研究这种变体在疾病进展中的预测作用及其对纤维化相关蛋白质表达的影响,对于了解中国患者的CD病原体至关重要.
研究的目的:
- 评估TNFSF15单核酸多态 rs6478109和中国人群中CD之间的关联.
- 评估这种基因变异对疾病进展的预测价值,特别是严格的表型.
- 检查TNFSF15基因型与纤维化相关蛋白质在阴茎粘膜中的表达之间的关系.
主要方法:
- 在428名CD患者和450名健康对照中,TNFSF15 rs6478109多态的基因定型.
- 进行基因型-表型相关性分析,以将遗传变异与疾病特征联系起来.
- 分析粘膜样本的TL1A和纤维化相关蛋白质表达,使用西方污染和免疫组织化学.
主要成果:
- 在CD患者 (63.3%) 中,rs6478109的G等位基因频率明显高于对照组 (46.7%).
- GG基因型与发展严格化表型 (HR=1.426) 的风险增加有关,并且在接受生物药物治疗的患者中显示出更强的关联 (HR=4.396).
- 与AA基因型相比,在GG基因型患者的内皮粘膜中观察到TL1A,亲纤维蛋白和TGFβ1/Smad3通路激活的增加表达.
结论:
- TNFSF15风险基因型GG与亲纤维蛋白的表达增加有关.
- 这种基因型可能会成为克罗恩病发展的预测因素.
- 了解TNFSF15在纤维化中的作用可能会导致针对性治疗,以严格治疗CD.
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