Genetic Approaches to Functional Gastrointestinal Disorders

Abstract

Functional gastrointestinal disorders are complex symptom-based disorders without agreed upon biomarkers or pathophysiology. A better understanding of the genetic architecture of these disorders would help to better identify their complex biology and explain the common comorbidity with other disorders of persistent pain, mood, and affect, as well as possibly make it possible to identify subgroups of patients who respond to customized therapies. In contrast to monogenic diseases, polygenic diseases and traits are characterized by the contribution of common variants in a large number of genes, as well as environmental factors, to the vulnerability of an individual. Family and twin studies have clearly established a genetic component in irritable bowel syndrome. Although candidate gene studies have identified a few gene polymorphisms that may be correlated with the syndrome, small sample size, lack of reproducibility in large data sets, and the unreliability of the clinical phenotype require caution when extrapolating to a major role of any of the reported polymorphisms in the pathophysiology of irritable bowel syndrome. Future progress in this area will require better characterization of intermediate phenotypes with large effect size for the clinical phenotype, as well as consideration of gene-gene, environment-gene (epigenetics), and sex-gene interactions, genome-wide association, and whole genome sequencing approaches in large data sets.

Irritable Bowel Syndrome: Methods, Mechanisms, and Pathophysiology. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome

“…The intermediate phenotypes most commonly used in IBS are colonic transit, colonic motility and compliance, and sensation thresholds and ratings. Details regarding the published gene polymorphisms associated with IBS, the magnitude and significance of the disease association, the sample size, and the replication of findings are summarized in an extensive review by Saito et al (97).…”

Prevalencia de síntomas de intestino irritable en población asistente a centros comerciales de Santiago de Chile

“…Las evidencias de un factor genético están basadas en estudios que muestran una mayor concordancia en gemelos monocigóti-cos, en comparación con gemelos dicigóticos 35,36 , aunque este hallazgo no ha sido confirmado en todos los estudios 37 .…”

“…Diferentes trabajos han asociado el SII al polimorfismo del transportador de la serotonina, IL-10, receptor de la colecistoquinina y otros 37,38 .…”

Elevation of natural killer cell activity and alleviation of mental stress by the consumption of yogurt containing Lactobacillus gasseri SBT2055 and Bifidobacterium longum SBT2928 in a double-blind, placebo-controlled clinical trial

“…Experimental data have shown that probiotics, by modifying the GI microbiome, can affect both the ENS and the central nervous system (CNS) in addition to their effects on the mucosal immune system (Azpiroz et al, 2007;Saito, Mitra, & Mayer, 2010). Many people are aware of the communication that occurs between the GI tract and the central nervous system, but fewer know about the ability of the CNS to influence the microbiota and conversely, the influence of microbiota on the brain and behavior.…”