Study of HLA Allele Frequencies Associated with Autoimmune Diseases in the Population of the Russian Federation

An important role in the pathogenesis of autoimmune diseases is assigned to genetic factors, such as genes of the major histocompatibility complex, tumor necrosis factor, interleukin-2 receptor alpha, CD40 surface antigen gene, etc. To date, a large amount of data has been accumulated that certain HLA alleles increase risk of developing a number of autoimmune diseases (type I diabetes, primary adrenal insufficiency, idiopathic hypoparathyroidism, Graves' disease, rheumatoid arthritis, systemic lupus erythematosus, celiac disease, multiple sclerosis, etc.). The association of risk of developing autoimmune diseases, their course, susceptibility to certain drugs and HLA has a pronounced cross-population character, which makes it necessary to study the distribution of alleles associated with autoimmune diseases and search for new markers of predisposition to them in specific populations. Within the framework of this study, the nature of HLA allele’s distribution associated with a number of autoimmune diseases in the conditionally healthy population of the Russian Federation was studied. We performed HLA typing of biological samples belonging to 33,430 conditionally healthy Russians from 54 regions of the country. The samples were typed at six major loci (HLA-A, -B, -C, -DPB1, -DQB1, -DRB1) based on the results of genome-wide sequencing using bioinformatic pipeline. HLA alleles were annotated according to the nomenclature IPD-IMGT/HLA v3.22.0 (10.2015) and v3.41.0 (07.2020). The study demonstrated a statistically significant moderate association between the number of reported cases of rheumatoid arthritis and the proportion of carriers of the DRB1*01:01, DRB1*04:01 alleles, as well as the incidence of multiple sclerosis and the level of carriers of DRB1*13:03, DRB1*15:01, DQB1*06:02 in the Russian regions.Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics Approval Statement: The study was conducted within the framework of the ethical aspects of the Declaration of Helsinki of the World Medical Association. The study protocol was approved at the meeting of the local ethical committee of FGBU CSP FMBA of Russia dated 28.12.2020.