Genetic research in patients with hepatitis B

In this study, we aimed to prospectively evaluate the patients, diagnosedearlier with active hepatitis B in the Clinic of Gastroenterology, Medical Faculty,Dicle university and to receive interferon alpha-2a and interferon alpha-2b therapies,in terms of pre-and post-treatment choromosomal abnormality, mitotic index and p53gene codon 72 polymorphism and compare the findings with controls.To that end a total of 58 patients with chronic active hepatitis B were dividedinto two subgroups, depending on the interferon therapy given. They were evaluatedin terms of pre-and post-treatment chromosome analysis and mitotic index. Inaddition, the controls that consisted of 30 healthy subjects who were consistent withpatients, age, sex, smoking and alcohol habits and who had not used medicine, werealso assessed for chromosomal analysis and mitotic index. For p53 gene codon 72polymorphism, all the patients and subjects in the control group were analysed priorto the treatment by PCR-RFLP technique.It was determined that the average value of choromosomal abnormality seenin lymphocyte cultures of patients with chronic active hepatitis B statistically wassignificantly higher than controls (p<0.05), whereas mitotic index waslower(p<0.001).As a result of analyses performed before starting the treatment with interferonalpha-2a and interferon alpha-2b, and at the end of the treatment that lasted 6months, it was determined that there was not any significant difference in terms ofmitotic index and choromosomal abnormality (p>0,05).When p53 gene codon 72 polymorphism was checked in patients with chronicactive hepatitis B and healthy controls, it was observed that homozygous prolingenotype was more common in patients with respect to controls, homozygousarginine frequency was rarer and that heterozygote frequency was not different. Itxiwas determined that this differentiation in genotype distributions of patients andcontrols was statistically significant (p<0,05).Both in patients with HBV and in healthy populations, the rate ofchoromosomal abnormality in lymphocyte cultures of controls and patientspossessing homozygous prolin genotype which is considered to be related tohepatocellular carcinoma risk was found to be significantly higher thanchoromosomal abnormality rate seen in the other genotypes (Arg/Pro and Arg/Arg)(p<0,05). It was also observed that there was not any significant difference betweenpatients and controls for mitotic index rates ( p>0,05).The findings optained as a result of the study have aroused the conviction thatchoromosomal abnormality rate was higher in lymphocyte cultures of patients witchronic active hepatitis B with respect to controls, while mitotic index was lower,and therefore, interferon alpha therapy applied at proper doses has not led to anyeffect in this respect.The fact that homozygous proline genotype rate was found to be low in controlgroup in terms of p53 gene codon 72 polymorphism, though high in patient groupand that choromosomal abnormality rate was high in individuals possessing thisgenotype has led to the conclusion that this variant could be considered a risk factorfor development of chronic active hepatitis B.More extensive studies are required to support these findings.Moreover, in those studies that we have planned to conduct, the relationshipbetween p53 gene codon 72 polymorphism and prognosis of the disease is alsothought to be take into account carefully.Keywords: hepatitis B, Chromosomal anomaly, mitotic index, p53 gene,polymorphism.