Abstract:
Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, is often comorbid with somatic pain and psychological disorders. Dysregulated signaling of brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), has been implicated in somatic-psychological symptoms in individuals with IBS. We investigated the association of 10 single-nucleotide polymorphisms (SNPs) in the regulatory 3\' untranslated region of neurotrophic receptor tyrosine kinase-2 (NTRK2) kinase domain-deficient truncated isoform (TrkB.T1) and BDNF Val66Met SNP with somatic and psychological symptoms and quality-of-life (QoL) in a cohort from the United States (IBS, n = 464; healthy controls, n = 156). We found that the homozygous recessive genotype (G/G) of rs2013566 in individuals with IBS is associated with worsened somatic symptoms, including headache, back pain, joint pain, muscle pain, and somatization as well as diminished sleep quality, energy level, and overall QoL. Validation using United Kingdom BioBank data confirmed the association of rs2013566 with an increased likelihood of headache. Several SNPs (rs1627784, rs1624327, and rs1147198) showed significant associations with muscle pain in our U.S. cohort. These 4 SNPs are predominantly located in H3K4Me1-enriched regions, suggesting their enhancer and/or transcription regulation potential. Our findings suggest that genetic variation within the 3\' untranslated region region of the TrkB.T1 isoform may contribute to comorbid conditions in individuals with IBS, resulting in a spectrum of somatic and psychological symptoms impacting their QoL. These findings advance our understanding of the genetic interaction between BDNF/TrkB pathways and somatic-psychological symptoms in IBS, highlighting the importance of further exploring this interaction for potential clinical applications. PERSPECTIVE: This study aims to understand the genetic effects on IBS-related symptoms across somatic, psychological, and quality-of-life (QoL) domains, validated by United Kingdom BioBank data. The rs2013566 homozygous recessive genotype correlates with worsened somatic symptoms and reduced QoL, emphasizing its clinical significance.
摘要:
肠易激综合征(IBS),一种肠-脑相互作用的障碍,通常与躯体疼痛和心理障碍并存。脑源性神经营养因子(BDNF)及其受体的异常信号调节,原肌球蛋白相关激酶B(TrkB),与IBS患者的躯体心理症状有关。我们研究了NTRK2(TrkB)激酶结构域缺陷型截短同种型(TrkB)的调节3'非翻译区(UTR)中10个单核苷酸多态性(SNP)的关联。T1)和BDNFVal66MetSNP具有躯体和心理症状以及来自美国(U.S.)的队列中的生活质量(IBSn=464;健康对照n=156)。我们发现,在IBS患者中rs2013566的纯合隐性基因型(G/G)与躯体症状恶化有关,包括头痛,背痛,关节痛,肌肉疼痛,躯体化以及睡眠质量下降,能量水平和整体生活质量。使用英国BioBank(UKBB)数据进行的验证证实了rs2013566与头痛可能性增加的关联。在我们的美国队列中,一些SNP(rs1627784,rs1624327,rs1147198)显示出与肌肉疼痛的显着关联。这4个SNP主要位于H3K4Me1富集区域,提示它们的增强子和/或转录调节潜力。我们的发现表明,TrkB的3'UTR区域内存在遗传变异。T1同工型可能导致IBS患者的合并症,导致一系列躯体和心理症状影响他们的生活质量。这些发现促进了我们对BDNF/TrkB通路与IBS躯体心理症状之间的遗传相互作用的理解。强调进一步探索这种相互作用对潜在临床应用的重要性。透视:本研究旨在了解对IBS相关症状的遗传影响,心理,和生活质量领域,由UKBB数据验证。rs2013566纯合隐性基因型与躯体症状恶化和生活质量下降相关。强调其临床意义。