B.S.Ilyassova

The Scientific Research Institute of Cardiology and Internal Diseases of Health Ministry of Kazakhstan

The role of inheritance of IL10 gene polymorphisms in the HBV infection outcome in the Kazakh population

The problem of chronic hepatitis B (CHB) is current problem in the case of their spreading, asymptomatically on the early stage and the heavy clinical picture and prognosis on their late stage. In Kazakhstan the epidemiology statistic rate of CHB is 3,9 per 100 000 of population (2009). The speed of progression of CHB to the cirrhosis depends on the multitude factors. Since individual variation in cytokine release is predominantly caused by polymorphisms near or within the genes [Ahn SH et al, 2000], heterogeneity of the candidate gene in HBV-infected patients serves as probable biomarker for influence the disease phenotypes. Several proinflammatory cytokines such as Th1 cytokines and TNFα have been identified as participating in the viral clearance and the host immune response to HBV. In the contrast, the Th2 cytokine IL10 serves as a potent inhibitor of Th1effector cells [Fiorentino DF et al, 1991]. In this study, we evaluated the effects of functionally relevant cytokine polymorphisms in the promoters of the IL-10 (-1082G/A, -819C/T, and -592C/A) genes on the course of HBV infection in the Kazakh population.

Material and methods: we have investigated 170 samples of the patients in CHB and 50 healthy volunteers. Of 170 patients, 56 were considered have asymptomatic clinic, normal level of serum ALT, negative of HBV DNA and positive of anti-HBe antibody results and 64 were found to have CHB and 50 have cirrhosis caused by CHB. Three biallelic polymorphisms in the IL-10 gene promoter were analyzed by sequencing in both directions using BigDye Terminator v3.1 Cycle sequencing Kit (Applied Biosystems, USA) (Picture 1)

Picture 1. PCR-products with the IL10 primers, samples NN 1-106

The results: The frequency of C/C genotype at position -592 of IL-10 gene promoter was not significant higher in the HBV DNA negative patients than in the persistence groups and than in health group. But in the group in CHB frequency of homozygotesC/C was significant higher than in the liver cirrhosis patients (15.1% vs 8.0%, P = 0.034) (Picture 2).

In the study of the distribution of the gene promoter -819 the T/T genotype significantly predominated in the cirrhosis patients that the another groups (p<0,001) (Picture 3).

Examination of the G/G genotype at position -1082 hasn’t showed its association with the persistent and progression of the HBV infection. The frequency of genotype A/A at the -1082 of IL-10 gene was significant in patients with the CHB and liver cirrhosis that in clearance of HBV-infection and control group (p<0,01) (Picture 4).

Conclution: Inheritance of the IL-10 gene promoter (-1082A/A, -819T/T) polymorphisms in Kazakh population is genetic factor to progression in chronic HBV infection. The frequency of heterozygote inheritance all of these polymorphisms of IL10 gene were found not significant different in the health group and the experimental groups of patients.