5006
Ahmed Abd-Rabou Abd-Rabou Mohamed
Study of Genetic Variations in Apoptotic Genes and Hormonal Level Alterations in Hepatitis C Patients
P53 rs 1042522 - Fas rs 1800682 – SNPs – HCV gentotype-4a – Response.
The hepatitis C virus (HCV), the main cause of morbidity and mortality, is endemic worldwide. HCV is most common in underdeveloped nations, with the highest prevalence rates in Egypt. The dual therapy with pegylated-interferon-α2b plus ribavirin has markedly improved the clinical outcome of HCV. P53 induces the expression of Fas for triggering apoptosis; an important mechanism for limiting viral replication. This study aims at investigating the impact of P53 rs 1042522 and Fas rs 1800682 genetic polymorphisms at 72 Arg/Pro and -670 A/G respectively on HCV genotype-4a susceptibility and treatment response. Two hundred and forty volunteers were enrolled in this study and divided into two major groups; the first group was 160 HCV infected patients group and the second group was 80 healthy controls group. HCV patients were sub-divided into two sub-groups; 86 sustained virological responders sub-group and 74 non-responders sub-group. Quantitation of HCV-RNA by qRT-PCR and histological scores were performed for every patient, as well as genotyping of HCV-RNA, P53 at 72 Arg/Pro, and Fas at -670 A/G polymorphisms were done for all subjects. It was resulted that F0/1-HCV patients (patients with no or mild hepatic fibrotic stages) have significant differences of P53 at 72 (Pro/Pro andArg/Arg) genotypes and dominant/recessive genetic models as well as Fas -670 A/A genotype and dominant genetic model compared to F3/4-HCV patients (patients with advanced hepatic fibrotic stages). Moreover, HCV patients have significant differences of P53 72 (Pro/Pro) genotype and recessive genetic model as well as Fas -670 A/A genotype and dominant genetic model compared to controls. Furthermore, P53 72 Pro homozygous genotype and allele have high significant increases, while Fas -670 A/A homozygous genotype and allele have high significant decreases when comparing non-responders with responders. Low prolactin, high total testosterone, and high growth hormone levels may provide promising biomarkers for early prediction of treatment response when associated with P53 rs 1042522 Pro/Pro or Fas rs 1800682 A/A genotypes. Itwas concluded that P53 rs 1042522 (Pro/Pro and Arg/Arg) genotypes and Fas rs 1800682 A/A genotype may be potentially used as sensitive genetic markers for HCV genotype-4a susceptibility. Finally, it was concluded that Pro variant of P53 rs 1042522 may be used as a polymorphic predictor for non-responsiveness, while A/A variant of Fas rs 1800682 may be used as a sensitive biomarker for responsiveness to antiviral therapy of HCV genotype-4a infection.
2015
Ph.d
Cairo
Science