Genetic factors and the course of irritable bowel syndrome: associations and interactions
Authors:   Omsk State Medical University, Omsk, Russian Federation, Gaus O.V. , Livzan M.A. ,   Omsk State Medical University, Omsk, Russian Federation
Published: July 2023

Aim: to evaluate the effect of the interaction of genetic and epigenetic factors on the formation and persistence of signs concerning irritable bowel syndrome (IBS). Patients and Methods: the study included 263 patients with IBS (189 female, 74 male, mean age — 29 [25; 35] years), including: IBS with diarrhea (n=84), IBS with constipation (n=92), mixed IBS (n=87); mild (n=110), moderate (n=99), severe (n=54) course. The control group consisted of 40 subjects comparable by gender and age. In each group, the polymorphism prevalence of candidate genes associated with IBS (COMT, DRD2, SLC6A4, LCT, FTO, TLR9), nutritional characteristics, the level of anxiety and depression, including specific gastrointestinal anxiety, life quality, cortisol content in saliva, blood serotonin, dopamine blood level, fecal zonulin. Results: Val/Val genotype of the COMT gene, characterized by high enzyme activity, was more common among patients with IBS with diarrhea and mixed IBS (χ2=55.75, p<0.001), in severe course (χ2=32.66, p<0.001) and was associated with diarrhea (χ2=53.39, p<0.001), anxiety (χ2=20.01, p<0.001); Met/Met genotype was associated with constipation (χ2=16.09, p<0.001), abdominal pain (χ2=11.04, p=0.004) and depression (χ2=13.12, p=0.001). T/T genotype of the DRD2 gene, leading to a decrease in the density of dopamine D2 receptors, was more commonly found in patients with IBS with constipation (χ2=13.05, p=0.042) and severe course (χ2=30.37, p<0.001), and was associated with abdominal pain (χ2=42.84, p<0.001), episodes of overeating (χ2=29.05, p<0.001), sugar cravings (χ2=16.82, p=0.002) and depression (χ2=39.63, p<0.001). S/S genotype of the SLC6A4 gene, leading to a decrease in serotonin reuptake, was more common in patients with IBS with diarrhea (χ2=28.77, p<0.001), and was associated with abdominal pain (χ2=9.15, p<0.001), diarrhea (χ2=39.98, p<0.001) and anxiety (χ2=7.87, p=0.02), genotype L/L — with constipation (χ2=12.4, p=0.002). A/A genotype of the FTO gene was associated with overweight (χ2=41.33, p<0.001), episodes of overeating (χ2=31.49, p<0.001), increased consumption of added sugar (χ2=9.25, p=0.010), and cravings for sweet (χ2=26.19, p=0.001), farinaceous and confectionery products (χ2=7.85, p=0.019). CC genotype of the TLR9 gene, leading to excessive activation of TLR9, was more commonly detected in individuals with a history of acute intestinal infection (χ2=8.45, p=0.038). Conclusion: the identified associations suggest the impact of genetic and environmental factors on the severity and nature of the IBS course. KEYWORDS: irritable bowel syndrome, genetic factors, epigenetic factors, catechol-O-methyltransferase, dopamine D2 receptors, serotonin reuptake transporter, fat mass and obesity-associated gene, LCT gene, toll-like receptors. FOR CITATION: Gaus O.V., Livzan M.A. Genetic factors and the course of irritable bowel syndrome: associations and interactions. Russian Medical Inquiry. 2023;7(5):237–248 (in Russ.). DOI: 10.32364/2587-6821-2023-7-5-1.