Molecular genetic markers of primary liver steatosis in the formation of non-alcoholic fatty liver disease

Abstract

Purpose of research. Study of the frequency of detection of mutations in the α1 -antitrypsin SERPINA1 gene in non-alcoholic fatty liver disease (NAFLD) in comparison with individuals from the General population and assessment of features of metabolic disorders.Materials and methods. 439 people were examined, including 114 patients with NAFLD and 325 individuals in the General population. All subjects were subjected to molecular genetic testing. The frequency of mutations of the Glu342Lys (PIZ) and Glu264Val (PIS) alleles of the serpina1 α1-antitrypsin gene was evaluated. All patients with NAFLD underwent a comprehensive examination, during which standard indicators of liver function, lipid, porphyrin metabolism and cytokine spectrum were determined.Results. Mutations of the α1 -antitrypsin SERPINA1 gene are signifi cantly more common in patients with NAFLD compared to individuals in the General population. Violations of lipid, porphyrin metabolism and cytokine spectrum parameters in the presence of mutations of the α1-antitrypsin SERPINA1 gene or their absence were registered with the same frequency. Against the background of mutations of the α1 -antitrypsin SERPINA1 gene, deviations from the normal values of lipid, porphyrin metabolism and cytokine spectrum were more signifi cant. Violations of porphyrin metabolism and cytokine spectrum were found in the majority of patients (in 69.4% and 77.1% of cases, respectively). Conclusion.Conducting molecular genetic studies in NAFLD allows you to clarify the degree of metabolic disorders and assess the prognosis of the disease.

HFE hemochromatosis gene polymorphism and porphyria cutanea tarda

“…На этом фоне часто наблюдается формирование стеатоза печени, который может трансформироваться в цирроз печени и существенно повышается риск развития гепатоцеллюлярной карциномы [13,23]. Показано, что при неалкогольной жировой болезни печени мутации в гене HFE регистрируются у 32%, а дисметаболизм порфиринов -у 65% больных [24,25,26]. Хроническая HCV-инфекция, частые алкогольные эксцессы и/или хроническая алкогольная интоксикация оценивается одним из совокупных условий, провоцирующих расстройства порфиринового обмена [27][28][29][30].…”

Identification of Pathogenic Variant Burden and Selection of Optimal Diagnostic Method Is a Way to Improve Carrier Screening for Autosomal Recessive Diseases

“…To find a balance between the size of the panel (and therefore cost of screening) and the proportion of carriers it allows to detect, it is necessary to know the AF in the target population [ 6 ]. We designed a custom panel for carrier screening of the four aforementioned diseases consisting of 115 variants, which occur in the Russian population according to the literature data [ 4 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. This custom panel was validated on the population-based sample, representing 1243 unrelated individuals from the Vologda region [ 8 ], as well on 350 volunteers interested in carrier screening.…”