TNFSF15 variant predicts disease progression in Chinese patients with Crohn's disease.

IF 3.8 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology Report Pub Date : 2024-11-11 eCollection Date: 2024-01-01 DOI:10.1093/gastro/goae103

Qi Zhang, Wei Wang, Bingjie Xiang, Dezheng Lin, Jun Hu, Junzhang Zhao, Jue Lin, Tao Liu, Jun Deng, Min Zhang, Min Zhi

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引用次数: 0

Abstract

Background: The genetic variant of tumor necrosis factor superfamily member 15 (TNFSF15) is associated with Crohn's disease (CD) and the development of intestinal fibrosis and stricturing. We aimed to investigate its predictive role in disease progression and the impact of ileal fibrosis-associated protein expression in Chinese patients with CD.

Methods: We genotyped the single nucleotide polymorphism rs6478109 within the TNFSF15 gene in 428 CD patients and 450 health controls to assess its association with CD. Genotype-phenotype correlation analyses were performed. Mucosal samples from non-diseased terminal ileum were analyzed for TL1A and fibrosis-associated protein expression using western blot and immunohistochemistry.

Results: The G allele frequency of rs6478109 was significantly higher among CD patients compared with health controls (63.3% vs. 46.7%, P < 0.001). Patients with GG genotype were more predisposed to develop the stricturing phenotype, compared with those with AA + AG genotypes with a hazard ratio of 1.426 (95% confidence interval: 1.029-1.977, P = 0.033). This trend was similarly observed in patients utilizing biological agents, with a hazard ratio of 4.396 (95% confidence interval: 1.780-10.854, P = 0.001). Furthermore, increased TL1A, pro-fibrotic proteins, and TGFβ1/Smad3 pathway activation were observed in non-diseased ileal mucosa of patients with GG genotype compared with those with AA genotype.

Conclusions: The TNFSF15 risk genotype GG could promote the expression of pro-fibrotic proteins and may serve as a predictor for stricturing CD.

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TNFSF15变异可预测中国克罗恩病患者的疾病进展。

背景：肿瘤坏死因子超家族成员15（TNFSF15）的基因变异与克罗恩病（CD）及肠纤维化和狭窄的发生有关。我们的目的是研究 TNFSF15 基因在中国 CD 患者疾病进展中的预测作用及其对回肠纤维化相关蛋白表达的影响：我们对 428 例 CD 患者和 450 例健康对照进行了 TNFSF15 基因内单核苷酸多态性 rs6478109 的基因分型，以评估其与 CD 的相关性。进行了基因型与表型的相关性分析。利用Western印迹和免疫组化技术分析了非病变回肠末端黏膜样本中TL1A和纤维化相关蛋白的表达情况：rs6478109的G等位基因频率在CD患者中明显高于健康对照组（63.3% vs. 46.7%，P 0.001）。与 AA + AG 基因型的患者相比，GG 基因型的患者更容易出现严格化表型，危险比为 1.426（95% 置信区间：1.029-1.977，P = 0.033）。在使用生物制剂的患者中也观察到类似的趋势，危险比为 4.396（95% 置信区间：1.780-10.854，P = 0.001）。此外，与 AA 基因型患者相比，在 GG 基因型患者未患病的回肠粘膜中观察到 TL1A、促纤维化蛋白和 TGFβ1/Smad3 通路激活增加：结论：TNFSF15风险基因型GG可促进促纤维化蛋白的表达，并可作为CD恶化的预测因子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gastroenterology Report Medicine-Gastroenterology

CiteScore

4.60

自引率

2.80%

发文量

审稿时长

8 weeks

期刊介绍： Gastroenterology Report is an international fully open access (OA) online only journal, covering all areas related to gastrointestinal sciences, including studies of the alimentary tract, liver, biliary, pancreas, enteral nutrition and related fields. The journal aims to publish high quality research articles on both basic and clinical gastroenterology, authoritative reviews that bring together new advances in the field, as well as commentaries and highlight pieces that provide expert analysis of topical issues.