Prevalence rate and prognostic value of the IL-28 gene polymorphism in hepatitis C patients in the Krasnodar territory

Abstract

Objective. The study of the prevalence rate of the IL-28B genotype polymorphism in chronic hepatitis C (CHC) patients in the Krasnodar territory for the prediction of the effectiveness of various schemes of antiviral therapy. Materials and methods. There was executed the determination of single nucleotide polymorphisms (SNP) at loci rs8099917 and rs12979860 of the IL-28B gene in 833 CHC genotype 1 patients, aged of from 18 to 73 years, living in the Krasnodar Territory. In 260 cases the viral load has been determined. For genotyping IL-28B there was used the method of allele-specific PCR test system «AmpliSens Genoskrin IL28B-FL» in a amplifier with system of detection offluorescent signal in real-time mode “Rotor-Gene Q” (“Qiagen”, Germany). The investigation of the marker rs12979860 study was performed in combination with the marker rs8099917. Combinations of genotypic variants SNPIL-28B were compared with the rate of early virological response (EVR) and Sustained Virological Response (SVR) under antiviral therapy comprised of two components IFN/ ribavirin (20) andPEG-IFN/ribavirin (68 patients), as well as the "triple therapy": PEG-IFN/RBV/inhibitorsprotease 1 and 2 generations (16 cases). Results and discussion. In the Krasnodar territory in CHC genotype 1 patients there is prevailed heterozygous variant rs12979860 CTIL-28B (58.3%), potentially unfavorable in the prescription of "double" therapy. The detection rate of the protective allele CC is 2.1 times less often (27.7%). In the rs8099917 locus there is dominatedfavorable TTgenotype (53.4%), slightly exceeding the frequency of heterozygous risk genotype GT (41.2%). The frequency of combinations of various protective genotypes (CC+CT), less favorable (CT+TT), the most unfavorable for the prognosis (CT+GT) for two interleukin 28B gene loci is about the same accounting of from 26.3 to 32%. Patients with protective CC+TT alleles had the significantly higher viral load if compared with a group of patients with unfavorable TT+GG homozygotes. In the treatment of CHC patients with genotype CC+CT in investigated loci (rs12979860 and rs8099917) according to such schemes as IFN/RBV and Peg-IFN/RBV, EVR was observed in 100% and SvR - in 89.4-849% ofpatients respectively. The combination of CT+TT alleles of the IL28B gene significantly reduced the effectiveness of treatment of PEG-IFN/RBV to 50%; in this process a combination of CT+GT heterozygotes has the highest proportion while SVR does not exceed 33.3%."Triple" therapy with PEG-IFN/RBV/ protease inhibitors of 1st and 2nd generations eliminates the significance of the combination of unfavorable genotypes SNP of the interleukin 28B gene, allowing to achieve EVR in all the patients with the absence of protective alleles CC+TT, SVR - in 85.7% of cases. Conclusion. In choosing treatment regimens for CHC genotype 1 patients the differentiated approach is appropriate, with taking into account the favorable and unfavorable combinations of genotypic variants of the IL28B gene concerning rs12979860 and rs8099917. In patients with the presence ofprotective alleles CC+TT on these loci, a "double" combination therapy by as pegylated as well standard interferon preparations with ribavirin is highly effective and may be preferred; in the combination of less favorable alleles CT+TT, and particularly unfavorable heterozygotes CT+GT ofIL-28B gene, it is advisable to use a "triple" therapy with PEG-IFN/RBV/protease inhibitors of 1st and 2nd generations or non-interferon regimens. The study of the distribution of SNP genotypes of IL28B genes and their combinations in CHC patients C allowed to evaluate rationally the need of that cohort ofpatients for various, including expensive non-interferon, therapy schemes.