SCN10A 多态性对克罗恩病和溃疡性结肠炎患者腹痛感知和内脏痛觉减退的影响

IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Clinical and Translational Gastroenterology Pub Date : 2024-10-17 DOI:10.14309/ctg.0000000000000778
Matthew D Coates, Vonn Walter, August Stuart, Jeffrey Small, Shannon Dalessio, Nurgul Carkaci-Salli, Ann Ouyang, Kofi Clarke, Andrew Tinsley, Emmanuelle D Williams, Piotr Janicki, Victor Ruiz-Velasco, Kent E Vrana
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引用次数: 0

摘要

导言:低痛觉炎症性肠病(IBD)可能为人类腹痛提供重要的启示。这种疾病以前与一种多态性(rs6795970,A1073V;1073val/val)的同源性有关,这种多态性与 Nav1.8 有关,Nav1.8 是一种电压门控钠通道,在痛觉感受器上优先表达。目前还不清楚克罗恩病(CD)和溃疡性结肠炎(UC)是否都存在这种关系。本研究评估了一个规模更大、表型更仔细的 IBD 队列,以探究这一问题:在同时评估肠道炎症状态和腹痛经历的研究队列中比较了 rs6795970 的等位基因和基因型频率。在健康人中使用直肠球囊扩张(RBD)法进行内脏感知:我们分析了 416 名 IBD 患者(261CD:155UC)和 142 名健康对照者。在 IBD 队列中,有 84 人(43CD:41UC)被确定患有低痛觉疾病。与其他 IBD 患者和健康对照组相比,低痛感 IBD 患者的 rs6795970 等位基因频率明显更高。与其他 IBD 患者和健康对照组相比,低镇痛 IBD 患者也更有可能是该多态性的同卵双生者。低痛感的 CD(30%vs.12%,p=0.004)和低痛感的 UC(32%vs.15%,p=0.036)都更有可能与 rs6795970 多态性的同源性有关。在一组健康人(n=50)中,rs6795970 同源基因携带者(n=11)也表现出对 RBD 的腹部不适感减少:这些研究结果表明,Nav1.8 在人类内脏痛觉中起着关键作用,可作为治疗低痛觉 CD 和 UC 的新型诊断靶点,以及慢性腹痛相关疾病的潜在治疗靶点。
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Impact of SCN10A Polymorphism on Abdominal Pain Perception and Visceral Hypoalgesia in Crohn's Disease and Ulcerative Colitis.

Introduction: Hypoalgesic inflammatory bowel disease (IBD) may provide critical insights into human abdominal pain. This condition was previously associated with homozygosity for a polymorphism (rs6795970,A1073V;1073val/val) related to Nav1.8, a voltage-gated sodium channel preferentially expressed on nociceptors. It was unclear whether this relationship existed for both Crohn's disease (CD) and ulcerative colitis (UC). This study evaluated a larger, carefully phenotyped IBD cohort to investigate this question.

Methods: Allelic and genotypic frequencies of rs6795970 were compared among study cohorts characterized by concomitant assessment of intestinal inflammatory status and abdominal pain experience. Visceral sensory perception was performed in healthy individuals using rectal balloon distension(RBD).

Results: We analyzed 416 IBD patients (261CD:155UC) and 142 healthy controls. In the IBD cohort, 84 individuals (43CD:41UC) were determined to have hypoalgesic disease. The allelic frequency of rs6795970 was significantly higher in hypoalgesic IBD patients when compared to other IBD patients and healthy controls. Hypoalgesic IBD patients were also more likely to be homozygous for this polymorphism when compared to other IBD patients and healthy controls. Hypoalgesic CD (30%vs.12%,p=0.004) and hypoalgesic UC (32%vs.15%,p=0.036) were each significantly more likely to be associated with homozygosity for the rs6795970 polymorphism. In a cohort of healthy individuals(n=50), rs6795970 homozygotes(n=11) also demonstrated reduced abdominal discomfort to RBD.

Discussion: These findings indicate that Nav1.8 plays a key role in human visceral pain perception, and could serve as a novel diagnostic target in the management of hypoalgesic CD and UC, and potential therapeutic target for conditions associated with chronic abdominal pain.

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来源期刊
Clinical and Translational Gastroenterology
Clinical and Translational Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
7.00
自引率
0.00%
发文量
114
审稿时长
16 weeks
期刊介绍: Clinical and Translational Gastroenterology (CTG), published on behalf of the American College of Gastroenterology (ACG), is a peer-reviewed open access online journal dedicated to innovative clinical work in the field of gastroenterology and hepatology. CTG hopes to fulfill an unmet need for clinicians and scientists by welcoming novel cohort studies, early-phase clinical trials, qualitative and quantitative epidemiologic research, hypothesis-generating research, studies of novel mechanisms and methodologies including public health interventions, and integration of approaches across organs and disciplines. CTG also welcomes hypothesis-generating small studies, methods papers, and translational research with clear applications to human physiology or disease. Colon and small bowel Endoscopy and novel diagnostics Esophagus Functional GI disorders Immunology of the GI tract Microbiology of the GI tract Inflammatory bowel disease Pancreas and biliary tract Liver Pathology Pediatrics Preventative medicine Nutrition/obesity Stomach.
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