MUTATIONS H1069Q OF ATP7B GENE AND C282Y AND H63D OF HFE GENE IN PERSONS WITH HEPATOBILARY DISEASES OF UNDEFINED GENESIS

Abstract

Wilson disease (WD) is an autosomal-recessive disorder of hepatocellular copper deposition caused by pathogenic variants ATP7B gene. Genetic testing of ATP7B gene is not usually used for Wilson’s disease (WD) diagnostics in Ukraine and due to the marked heterogeneity in clinical presentation the diagnosis of WD remains challenging. Hereditary hemochromatosis is an autosomal-recesive pathology coused by mutations in HFE gene. The most common mutations in this gene are H63D and C282Y. Effective therapy is developed for hemochromatosis and Wilson’s Diseases, but these pathologies still appear to be in the late stages, which is associated with nonspecific manifestations. Aim. To establish the prevalence of H1069Q mutations of the ATP7B, C282Y and H63D of the HFE gene and the contribution of hereditary hemochromatosis (HH) and Wilson’s disease (WD) into the etiology of idiopathic hepatobiliary disorders. Methods. DNA was isolated from blood samples using a modified salting out method. Detection of H63D and C282Y mutations of HFE gene was carried out using PCR and restriction fragment length polymorphism analysis, H1069Q by BI PASA analysis and detected by agarose electrophoresis. Results. 28.57% of the subjects were carriers of H63D mutation of HFE gene, 13.44% – carriers of C282Y mutation of the HFE gene but only one case of HH was confirmed. H1069Q mutation of ATP7B gene was detected in 4.0% cases which were confirmed as WD diagnosis. Such results are due to a significant higher population frequency of mutations in the HFE gene compared to ATP7B. Conclusions. The detection four times more cases of WD compared with the HH indicates a greater contribution of WD to the etiology of idiopathic hepatobiliary disorders, compared to HH.

Keywords

• ATP7B gene
• HFE gene
• Wilson’s disease
• hereditary hemochromatosis
• idiopathic hepatitis.