Interaction of polymorphism of the interleukin-6 gene with immunological damages and their role in the development of mixed cryoglobulinemia in patients with chronic hepatitis C

Abstract

Aim. To determine the role of the relationship of immunological disorders with interleukin-6 gene polymorphism in the formation of HCV-associated mixed cryoglobulinemia. Materials and methods. The study included 149 patients with chronic hepatitis C. The polymorphism of the IL-6 gene (rs1800795) was determined by the method of polymerase chain reaction, the quantitative content of IL-6, RF IgM and IgG by enzyme immunoassay, cryoglobulins by spectrophotometric method. The patients were divided into groups depending on the polymorphism of the IL-6 gene and the presence of mixed cryoglobulinemia. Results. The frequency of formation of HCV-associated mixed cryoglobulinemia depended on the polymorphism of the IL-6 gene. In patients with chronic hepatitis C with mixed cryoglobulinemia, the frequency of registration of the CC genotype of the IL-6 gene was lower than in patients without mixed cryoglobulinemia, namely, in 9.7 % versus 28.6 % of patients. The presence of the G-allele, namely the CG/GG genotypes of the IL-6 gene polymorphism, was more often detected in patients with mixed cryoglobulinemia, namely, in 90.3 % of patients against 71.4 % of patients without signs of mixed cryoglobulinemia (χ 2 = 8.94, P = 0.003). In the presence of G-allele, the quantitative content of IL-6 inthe serum of the general group of patients with CHC was higher than in healthy people (P 0.05). The highest levels of IL-6 were recorded in patients with HCV-associated mixed cryoglobulinemia who had the G-allele. The content of IL-6 in the blood serum of these patients exceeded the indicators of both healthy people (P < 0.001) and the results of patients without mixed cryoglobulinemia (P < 0.01). In patients with chronic hepatitis C with mixed cryoglobulinemia, even in the presence of the CC genotype, the content of IL-6 in serum was higher both in comparison with healthy (P < 0.01) and in comparison with patients without signs of this extrahepatic manifestation (P < 0.01). In patients with chronic hepatitis C with mixed cryoglobulinemia, the presence of CG/GG genotypes was associated not only with the highest serum IL-6 content, but also with the presence of more pronounced autoimmune disorders due to a higher content of RF IgM (P = 0.04) and mixed cryoglobulins (P = 0.03) in serum, in comparison with patients who had the CC genotype. Moreover, the presence of more pronounced immune disorders in patients with HCV-associated mixed cryoglobulinemia in the presence of CG/GG genotypes was accompanied by more frequent manifestation of severe general weakness (P = 0.003), arthralgia (P = 0.02) and the formation of Meltzer’s triad. Conclusion. The frequency of detection of the G-allele, namely the CG/GG genotypes of the IL-6 gene polymorphism, is the highest in patients with HCV-associated mixed cryoglobulinemia (90.3 %). The presence of CG/GG genotypes in patients with chronic hepatitis C with mixed cryoglobulinemia contributes to more pronounced immunological disorders due to the highest content of IL-6, mixed cryoglobulins, and RF IgM in serum, which causes the manifestation of the clinical symptoms of this hepatic manifestation.