Genetic Factors for the Natural Elimination of Hepatitis C Virus

N. V. Vlasenko, T. A. Loscutova, K. Mironov, A. Esman, E. Dunaeva, T. Semenenko, D. B. Dubodelov, M. Korabelnikova, Z. Ponezheva, V. Makashova, K. Omarova, A. V. Sacuk, G. Solopova, S. Kuzin, V. Akimkin
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Abstract

Relevance. The identification of determinants of the human genome, such as single nucleotide polymorphisms (SNPs), in association with various disease patterns, including infectious diseases, is one of the most actively developing areas of scientific research in the world..  Hepatitis C (HC), which remains a serious global health problem, belongs to the number of infections that attract the attention of specialists.Aims. Determination of genetic markers of hepatitis C virus (HCV) natural elimination and assessment of their role as a monitoring parameter of the epidemiological surveillance system.Materials and methods. The study included 660 people divided into 2 groups: persons with chronic HC (CHC) and blood donors (indicator group of the healthy population). In the studied groups, the following SNPs were typed: rs1143634, rs1143627 (IL-1B); rs4251961, rs419598 (IL1RN); rs1800795 (IL6); rs1800896 (IL-10); rs4986790 (TLR4); rs4374383 (MERTK). The associative relationship between SNPs and CHC alleles was identified using logistic regression analysis within four models (codominant, dominant, recessive, and overdominant). Additionally, the significance of polymorphisms at the intragenic and intergenic levels was assessed using modern bioinformatic resources in the field of functional genomics.Results. In this study, genotypes associated with the natural elimination of HCV were identified. Paired combinations of IL 1RA/IL-1B genotypes associated with the probability of the formation of CHC have been established. It is shown that synonymous SNPs can be associated with any characteristics of the pathological process, which can be explained by disequilibrium in coupling with functionally significant alleles of other genetic loci.Conclusion. The detection of the association of SNPs with clinical manifestations of the pathological process is not final and requires further study taking into account ONP coupling groups.
自然消除丙型肝炎病毒的遗传因素
的相关性。鉴定人类基因组的决定因素,如与各种疾病模式(包括传染病)有关的单核苷酸多态性(SNPs),是世界上发展最活跃的科学研究领域之一。丙型肝炎(HC)仍然是一个严重的全球健康问题,属于引起专家注意的感染数量。丙型肝炎病毒(HCV)自然消除遗传标记的测定及其作为流行病学监测系统监测参数的作用评估材料和方法。研究纳入660人,分为2组:慢性HC (CHC)患者和献血者(健康人群指标组)。在研究组中,对以下snp进行了分型:rs1143634, rs1143627 (IL-1B);rs4251961, rs419598 (IL1RN);rs1800795(白细胞介素6);rs1800896 (il - 10);rs4986790 (TLR4);rs4374383 (MERTK)。在共显性、显性、隐性和超显性四种模型中,通过logistic回归分析确定snp与CHC等位基因之间的关联关系。此外,利用功能基因组学领域的现代生物信息学资源,评估了基因内和基因间多态性的意义。在这项研究中,确定了与HCV自然消除相关的基因型。已经建立了与CHC形成概率相关的IL 1RA/IL- 1b基因型配对组合。结果表明,同义snp可以与病理过程的任何特征相关联,这可以解释为与其他遗传位点的功能显著等位基因偶联的不平衡。检测snp与病理过程的临床表现的关系并不是最终的,需要进一步研究考虑到ONP偶联组。
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