ABSTRACT
Based on population analysis of the DRB1, DQA1, DQB1 and TNFA allele frequency distribution patterns, regional features of immunogenetic structure of the population of West Siberia were investigated. Statistically significant linkage disequilibrium within the HLA class II region, as well as between the TNFA and DRB1, DQA1, and DQB1 was demonstrated. Population frequency distribution patterns of two- and multilocus haplotypes were examined.
Subject(s)
Emigration and Immigration , Gene Frequency/genetics , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Tumor Necrosis Factor-alpha/genetics , Alleles , Female , HLA-DQ alpha-Chains , HLA-DQ beta-Chains , HLA-DRB1 Chains , Haplotypes/genetics , Humans , Linkage Disequilibrium/genetics , Male , Moscow , SiberiaABSTRACT
Study of the pathogenesis of viral hepatitis C is of primary importance because of persistence of this virus and high incidence of chronic course of this disease, and as a consequence, development of cirrhotic and neoplastic processes in the liver determining high mortality from this condition. Proinflammatory cytokines, in particular, tumor necrosis factor, play an important role in the development of these pathological processes. The content of tumor necrosis factor in the circulating blood plasma and hepatocytes increases in acute and chronic hepatitis C. It seems that the capacity of cells to produce proinflammatory IL in high or low levels spontaneously or after antigenic stimulation largely determines the outcome of infectious process in contact with the virus.
Subject(s)
Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/immunology , Polymorphism, Genetic , Promoter Regions, Genetic , Tumor Necrosis Factor-alpha/genetics , Alleles , Case-Control Studies , Gene Frequency , Genotype , Humans , SiberiaABSTRACT
The distribution of allele variants of promotor sites of interleukins 4 (C-590T) and 10 (C-597A) and tumor necrosis factor-alpha (G-308A) genes was studied in HIV-infected patients and normal subjects of the Europeoid population in Russia. Some deviations in the distribution of genotypes of the studied polymorphism were revealed in HIV-infected patients compared to the control. The distribution of genotypes in these groups is different for men and women, which is significant for inheritance of allele variants of the cytokine gene.
Subject(s)
HIV Infections/genetics , Interleukin-10/genetics , Interleukin-4/genetics , Polymorphism, Genetic , Promoter Regions, Genetic , Tumor Necrosis Factor-alpha/genetics , Adolescent , Adult , Female , Homozygote , Humans , Male , Middle AgedABSTRACT
The distribution of the allel variants of the promoter area (C = 590T) of the interleukin-4 (IL-4) gene in HIV-infected and relatively healthy representatives of the Caucasoid population has been studied. The relationship between the genotypes of this polymorphism and the production of IL-4 by mononuclear cells of peripheral blood as well as distribution of IL-4 genotypes among males and females is analyzed. The occurrence of the homozygous combination of the allel variant C/C of the promoter of IL-4 has been shown to prevail almost twofold over the occurrence of the variant C/T among healthy donors and HIV-infected patients. Sexual differences play an essential role in the character of inheriting the allel variants of the genes of IL-4, the presence of the homozygous variant C/C or T/T being a risk factor of HIV infection in males. As revealed in this study, in the peripheral blood of healthy donors mononuclear cells having genotype C/C differ from cells with the heterozygous variant C/T in higher spontaneous production of IL-4 and, simultaneously, in lower capacity for the activation of its production in response to stimulation with mitogen. In HIV-infected patients mononuclear cells differ in higher spontaneous production of IL-4 in comparison with controls. We may thus infer that the human genotype controlling the initial level of the production of IL-4 by lymphocytes Th2 may influence the intensity of antibody production in the process of infection.