The following is a summary of “Genetic Variations in TrkB.T1 Isoform and Their Association with Somatic and Psychological Symptoms in Individuals with IBS,” published in the July 2024 issue of Pain by Hong et al.

Irritable bowel syndrome (IBS), a gut-brain interaction disorder, coexists with somatic pain and psychological issues linked to disrupted brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) signaling.

Researchers conducted a retrospective study exploring the relationship between specific genetic variants in the BDNF and TrkB pathways and the somatic and psychological symptoms experienced by individuals with IBS.

They examined the association of 10 single nucleotide polymorphisms (SNPs) in the regulatory 3′ untranslated region (UTR) of the NTRK2 gene, which encodes the truncated isoform TrkB.T1, along with the BDNF Val66Met SNP. The study involved a cohort from the U.S., comprising 464 patients with IBS and 156 HCs.

The result showed that the homozygous recessive genotype (G/G) of a specific genetic variant (rs2013566) in patients with IBS was linked to increased somatic symptoms, such as headaches, back pain, joint pain, muscle pain, and somatization, along with reduced sleep quality, energy levels, and overall quality of life. The data validated from the U.K. Biobank confirms a connection between rs2013566 and a greater chance of headaches. Additionally, in the U.S. cohort, several SNPs, including rs1627784, rs1624327, and rs1147198, were related to muscle pain. The SNPs were primarily located in H3K4Me1-enriched regions, indicating the potential role in enhancer activity or transcriptional regulation.

Investigators concluded that genetic variations in the 3’UTR of the TrkB.T1 isoform may play a role in comorbid IBS conditions, affecting both somatic and psychological symptoms, underscoring the need for further research into the BDNF/TrkB pathways for potential clinical relevance.

Source: jpain.org/article/S1526-5900(24)00582-0/abstract#%20