RESUMEN
BACKGROUND: Hepatitis C virus (HCV) evolution is thought to proceed by mutations within the six major genotypes. Studies of HCV recombinant genotypes in different parts of the world have recently been initiated. Only a few cases of recombination have been identified worldwide, predominantly in Eastern Europe and Asia. In 2011 we detected the recombinant form (RF) of a HCV genotype RF_2k/1b in Georgia. Therefore, we reviewed HCV genotyping data of 491 patients with chronic hepatitis C virus infections of our center in Tbilisi over a period of two years. METHODS: Initially all genotyping analyses were performed with the VERSANT HCV genotype assay (Siemens, LiPA). In a second analysis, parts of the core and the NS5B region were sequenced for all HCV genotypes 2a/2c. RESULTS: Approximately 2/3 of genotype 2 cases were identified as the recombinant form HCV-RF 2k/1b. Overall, this type represented 19% of all HCV patients who underwent genotyping. CONCLUSIONS: We can conclude that almost 20% of HCV infected Georgian patients are infected with HCVRF_2k/ 1b.
Asunto(s)
Genotipo , Hepacivirus/genética , Hepatitis C Crónica/virología , Virus Reordenados/genética , Adulto , Anciano , Femenino , Georgia (República) , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Experimental evidence has been provided that a histidine-loop within the nucleotide binding domain of ABC transporter is essential for efficient function of this class of transporter proteins. Here we report the first patient with a mutation of the putative histidine-loop of a human ABC transporter, the multi drug resistance protein 3 (MDR3). The patient presented at the age of 4 years with a history of severe pruritus, elevated serum gamma-glutamyltransferase and bile acid levels since several years suggesting the diagnosis of progressive familial intrahepatic cholestasis type 3 (PFIC-3) due to defects in MDR3. Liver biopsy demonstrated an apparently normal MDR3 expression, however, genetic analysis revealed a novel homozygous mutation in the ABCB4 gene (c.3691C>T) in the patient. This mutation was associated with a change of histidine to tyrosine at amino acid position 1231 of MDR3 (p.H1231Y). As shown by sequence alignment, this amino acid corresponds to the highly conserved histidine of the "H-loop", which is critical for ATP-hydrolysis, suggesting an essential role of histidine 1231 of human MDR3.