Department of Biobehavioral Health Sciences, University of Pennsylvania School of Nursing, Philadelphia, PA.
Department of Pain and Translational Symptom Science, University of Maryland School of Nursing, Baltimore, MD.
J Pain. 2024 Nov;25(11):104634. doi: 10.1016/j.jpain.2024.104634. Epub 2024 Jul 14.
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.
肠易激综合征（IBS）是一种肠脑相互作用紊乱的疾病，常伴有躯体疼痛和心理障碍。脑源性神经营养因子（BDNF）及其受体原肌球蛋白相关激酶 B（TrkB）的信号调节异常与 IBS 患者的躯体-心理症状有关。我们研究了神经营养受体酪氨酸激酶-2（NTRK2）激酶结构域缺失的截断异构体（TrkB.T1）和 BDNF Val66Met SNP 的调节 3'非翻译区的 10 个单核苷酸多态性（SNP）与美国队列中躯体和心理症状以及生活质量（QoL）的关系（IBS，n=464；健康对照组，n=156）。我们发现，IBS 个体的 rs2013566 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、肌肉痛和躯体化，以及睡眠质量、能量水平和整体 QoL 下降。使用英国生物银行数据进行验证证实了 rs2013566 与头痛发生几率增加的关联。几个 SNP（rs1627784、rs1624327 和 rs1147198）在我们的美国队列中与肌肉疼痛有显著关联。这 4 个 SNP 主要位于 H3K4Me1 富集区域，表明它们具有增强子和/或转录调节的潜力。我们的研究结果表明，TrkB.T1 异构体 3'非翻译区的遗传变异可能导致 IBS 患者合并症的发生，从而导致一系列影响其 QoL 的躯体和心理症状。这些发现加深了我们对 BDNF/TrkB 通路与 IBS 中躯体-心理症状遗传相互作用的理解，突出了进一步探索这种相互作用以潜在应用于临床的重要性。观点：本研究旨在通过英国生物银行数据验证，了解与躯体、心理和生活质量（QoL）相关的 IBS 相关症状的遗传影响。rs2013566 纯合隐性基因型与躯体症状恶化和 QoL 降低相关，强调其临床意义。
