FREQUENCY OF MUTATIONS IN ABCB1 AND ABCB11 GENES IN PATIENTS WITH CHRONIC HEPATITIS C (HCV) IN RIO DE JANEIRO

Abstract

The post-COVID-19 syndrome is characterized by the appearance of symptoms and sequelae up to four weeks after the acute symptoms of COVID-19 and can affect various systems, such as respiratory, hematological and hepatic. Cases of chronic fatigue, thromboembolism events, myalgia and the increase in enzymes associated with liver damage have been reported. It is known that individuals with chronic liver disease, cirrhosis and/or hepatocellular carcinoma are more likely to develop post-COVID-19 syndrome. In addition, mutations in the ABCB1 gene (G2677T, C3435T and C1236T) that encode the drug-export pump (P-glycoprotein) are associated with drug resistance and hepatotoxicity. The T1331C mutation in the ABCB11 gene encodes the bile salt-exporting pump and is associated with cholestasis. Therefore, these mutations may be an aggravating factor for the post-COVID-19 syndrome, especially in hepatocompromised individuals. The aim of this study was to assess the frequencies of mutations in the ABCB1 and ABCB11 genes and to monitor the post-COVID-19 syndrome in patients with liver disease. We analyzed 197 samples from patients with chronic hepatitis C from the Liver Disease Outpatient Clinic of the Gaffrée and Guinle University Hospital. Extraction and mutation analysis by qPCR was performed using TaqMan Assays. In the ABCB1 gene, the most frequent mutation was C3435T (rs1045642) in 13.7% (TT), in this group 40.1% were wild-type (CC) and 46.2% were heterozygous (CT). For the C1236T (rs1128503) the frequency of wild-type (CC) was 45.2%, of heterozygotes (CT) 43.6% and mutants (TT) 11.2%. The lowest frequency of mutations in the ABCB1 gene was G2677T (rs2032582) in 8.6% of patients, 52.8% are wild-type (GG) and 38.6% are heterozygous (GT). As for the T1331C (rs2287622) in the ABCB11 gene, most individuals were heterozygotes ‒ TC (51.8%), followed by wild-type ‒ TT (34.0%) and mutants ‒ CC (14.2%). This is the first study to evaluate the association of cases and severity of post-COVID-19 syndrome with mutations in the ABCB1 and ABCB11. So far, there are only reports in the literature of the association of this mutations with liver damage and resistance to drugs used in the treatment of COVID-19, such as lopinavir and dexamethasone. Therefore, the presence of these mutations could influence the presence of the post-COVID-19 syndrome. We observed a greater presence of heterozygous individuals than the other genotypes in the population studied. It is necessary to investigate its association with cases of post-COVID-19 syndrome in hepatocompromised patients, in order to establish the risks associated with the syndrome in these individuals and to understand the influence of these polymorphisms on the clinical picture and evolution of these individuals. CAPES and FAPERJ.