Genetics of human gastrointestinal sensation

Purpose The objective was to review the genetics of human visceral pain with particular emphasis on pain associated with irritable bowel syndrome. Background The biomarkers most commonly employed in identifying visceral hypersensitivity are sensation ratings and thresholds or brain imaging during viscus (e.g., rectal) distension. Genetic studies suggest that variation in the control of candidate genes involved in ion channel function, neurotransmitter synthesis, reuptake or receptor functions, and inflammatory disease susceptibility loci may impact variations in prevalence of the symptom phenotype of abdominal pain or IBS, or quantitative traits (intermediate phenotypes) of rectal sensation. The candidate genes include SLC6A4, CNR1, and TNFSF15 reflecting serotonin reuptake, cannabinoid receptors, and inflammatory-barrier functions. However, other than TNFSF15, the other candidate genes are only univariately associated with pain, IBS symptom complex, or quantitative traits of sensation. These data have generated hypotheses and present opportunities for study of mechanisms and treatment of visceral pain in humans, which remains an unmet clinical need in patients with IBS and functional abdominal pain.