Clinical significance of genetic testing in ulcerative colitis and Crohn's disease
Authors: Rybachkov V. V. , Dryazhenkov I. G. , Sorogin S. A. , Bereznyak N. V. , Teviashov A. V. 
Published: September 2023

Relevance. Defects of innate and acquired immunity, intestinal microflora disorders, environmental factors against the background of genetic predisposition play a role in the development of ulcerative colitis and Crohn's disease. The question of the influence of genetic factors on the appearance of these diseases remains open. The purpose of the study. To develop approaches to assessing the course of ulcerative colitis and Crohn's disease, taking into account mutations of genes regulating tumor necrosis factor (TNF-a), vascular endothelial growth factor (VEGFA), interleukin-6 (IL-6) and polymorphic variants of the CARD15/NOD2 gene (Gly908Arg, Leu3020insC). Materials and methods. Polymorphic gene variants were studied in 50 patients with ulcerative colitis aged 18 to 79 years, 28 men (56%) and 22 women (44%). Age: under 35 years (38%), from 36 to 50 years (30%), over 51 years (32%). According to the extent of the pathological process, patients with total colitis prevailed (84%). Patients with left-sided colitis (14%) or proctitis (2%) were less common. In 28 patients (56%), chronic continuous course was observed, in 14 (28%) — chronic recurrent, in 8 (16%) — acute course. According to the severity of the attack: moderate (42%), light (28%) and heavy (32%) attacks were observed less frequently. Among the examined patients, surgical intervention was performed in 8 patients (16%), the remaining patients (84%) were treated conservatively. The diagnosis of ulcerative colitis was made on the basis of clinic data, ultrasound, colonoscopy, visual assessment of the pathological process during surgery and histological examination of the surgical material. The frequency of two polymorphic variants of the CARD15/NOD2 gene (Gly908Arg, Leu3020insC) was studied in 40 patients with Crohn's disease. All patients were admitted to the surgical hospital in an emergency. The diagnosis of Crohn's disease was made on the basis of clinic data, ultrasound examination, visual assessment of the pathological process during surgery and histological examination of the surgical material. The studies were conducted within a period of 1 to 10 years from the moment of discharge from the hospital. Results. In ulcerative colitis, mutations of the gene encoding IL-6 for the homozygous variant G174G occurred in 24%, mutations of the gene encoding VEGFA for the homozygous variant C634C occurred with a frequency of 12%. Mutations in the gene encoding tumor necrosis factor (TNF-α) were not detected in the study group. IL-6 gene mutation is almost equally found among groups of patients who underwent surgery and patients after conservative treatment, namely in 25% and 23.8%, respectively. However, mutations of the VEGFA gene were significantly more common (p=0.03) among patients with a history of surgical treatment (37.5%). Genetic testing in patients with ulcerative colitis makes it possible to predict the effectiveness of therapeutic measures, the likelihood of an increased risk of surgical treatment and can act as one of the criteria for the implementation of a personalized approach in this contingent of patients. In patients with Crohn's disease, polymorphisms of the CARD15/NOD2 gene according to the heterozygous variant occurred with a frequency of 35%, polymorphic variant Leu3020insC in 30% of patients, Gly908Arg in 2.5% of cases. Both polymorphic variants were observed in 2.5% of patients. The polymorphic variant Leu3020insC is associated with the localization of a pathological focus and dominates inflammation in the area of the ileocecal angle. Conclusions. In ulcerative colitis, the frequency of IL-6 gene mutations reaches 24%. Mutations of the VEGFA gene were 2 times less common (12%). Mutations in the TNF-α gene were not detected. It was found that mutations in the IL-6 gene are more common among male patients older than 51 years. According to the length of the process, IL-6 gene mutations are associated with left-sided colitis, and EGFR mutations with total intestinal damage. Mutation of the VEGFA gene to a certain extent may indicate the likelihood of an increased risk of surgical treatment. In Crohn's disease, the frequency of gene polymorphism reaches 35%. The polymorphic variant Leu3020insC is associated with the localization of a pathological focus and dominates inflammation in the area of the ileocecal angle. The appearance of a polymorphic variant of Gly908Arg to a certain extent may indicate a possible relapse of the disease.