Immunogenetic profile of MIC (A, B) HLA loci linked to MHC antigenic complex in Russians of the Chelyabinsk Region

Abstract

The MIC genes are located on chromosome 6 in the class I major histocompatibility complex (MHC) region and encode a membrane-bound stress-inducible protein that acts as a ligand to stimulate the NKG2D activating receptor expressed on the surface of the most natural killer cells (NK). Currently, 7 MIC loci are known, of which only MICA and MICB encode proteins and show a significant allelic polymorphism. The MIC gene polymorphism and their location in the HLA region suggests presence of some ethnic and populational differences for the gene frequencies, linkage disequilibrium of distinct loci, and distribution of HLA-MIC haplotypes, thus making it possible to get information on genetic relationship of human populations. The aim of our study was to assess immunogenetic profile of Russian population in Chelyabinsk Region based on the non-classical HLA loci, i.e., MICA and MICB, in the context of worldwide population data. Methods of the study included immunogenetic typing of 100 donors identifying themselves as Russians, taken from the Registry of Stem Cell Donors at the Chelyabinsk Regional Blood Transfusion Station. The 2 loci (MICA and MICB) were typed at basic resolution, using PCR technique with sequence-specific primers (SSP-PCR). Gene frequencies (GF) were calculated using programs for immunogenetic research (Arlequin 3.5).Among Russian population from Chelyabinsk Region, the following characteristics of the MICA gene distributions were found: MICA *008, *002, *010, *009, frequency of > 7%; average frequencies, for MICA *004, *007, *018, *017; whereas MICA *027, *011, *006, *009:02, *049, *012, *016 was registered at a frequency of < 3.5%. MICB gene profile was as follows: MICB *005:02, *004, *002, *008 at a frequency of > 6%; at a frequency of 4% MICB *003, *005:03; MICB *005:01, * 005:04, * 009N, MICB *013, *014 at a frequency of0.5%. As based on calculated genetic distances (according to Ney) for the MICA locus, the dendrogram and scatter plot were designed by means of multidimensional scaling (MDS) method, presenting location of 30 world populations, including data on Russians in Chelyabinsk Region. The smallest genetic distances between the population of Russians from Chelyabinsk Region and other world populations were found between the population of Slovenia, as well as the USA population of European origin. As based on scatterplot obtained by the MDS approach for MICA gene frequencies, using the data of cluster analysis, we have found that the population of Russians from Chelyabinsk Region belongs to a cluster of typical European populations.The obtained patterns could be used for practical purposes to create a registry of stem cell donors in Russia. In addition, the data may be used as a control group for further research in the area of HLA-disease association, and could be also demanded by the specialists in population ethnogenesis.