High frequency of the 472AA COMT (Val158) homozygous genotype of the catechol-O-methyltransferase (COMT) gene in children with irritable bowel syndrome

Abstract

Following the biopsychosocial model of medicine, the pathophysiological basis of irritable bowel syndrome (IBS) is a combination of biological, psychoemotional, and psychosocial factors, the contribution of each of them to the development of this disorder remains unclear. Psychoemotinal factors, which are involved in the pathogenesis of IBS, are caused not only by the environment but also by the metabolism of catecholamines, particularly by the functional activity of catechol-O-methyltransferase (COMT).

Purpose - to determine the role of Val158Met COMT polymorphism in development of IBS in children; to identify associations between genotype and clinical variant of the disorder and the nature of the provoking factor.

Materials and methods. The material for the molecular genetic study were DNA samples obtained from nuclear cells of venous blood of 54 patients aged 6-12 years with diagnosed IBS. In 48 practically healthy children of the same age DNA samples were isolated from buccal epithelial cells. Molecular genetic study of single nucleotide polymorphism rs4680 of COMT gene was performed by polymerase chain reaction followed by analysis of restriction fragment length polymorphism. Microsoft Excel 2016 and GraphPad Prism 5 software were used for statistical analysis.

Results. We have revealed significant differences in the distribution of Val158Met COMT genotypes in children with IBS in comparison with the control group. There was established that the 472GА COMT is more prevalent in healthy children and has a protective role in the development of IBS. In contrast, homozygous genotypes 472GG and 472AA, which are associated with changes in functional activity of enzyme COMT, may be considered as the risk factors for IBS (p≤0.0001).

Conclusions. Genotype 472АА COMT was mostly detected in сhildren with stress-associated IBS, which is more related to dysnociception, disorders of cognition, and emotional disturbances. The higher prevalence of 472GA COMT heterozygotes among children with postinfectious IBS and IBS associated with antibiotic therapy indicates a less important role for the psychoemotional component and nociceptive disorders in the onset of this disorder (p=0.03).

The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies.

No conflict of interests was declared by the authors.