mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-IPO-2324mimmun-2324Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESИммуногенетический профиль локусов, сцепленных с главным комплексом тканевой совместимости MHC (HLA) – MIC (MICA, MICB) у русских Челябинской областиImmunogenetic profile of MIC (A, B) HLA loci linked to MHC antigenic complex in Russians of the Chelyabinsk RegionБурмистроваА. Л.BurmistrovaA. L.

Д.м.н., профессор, заведующая кафедрой микробиологии, иммунологии и общей биологии биологического факультета

г. Челябинск

PhD, MD (Medicine), Professor, Head, Department of Microbiology, Immunology and General Biology, Faculty of Biology

Chelyabinsk

burmal@csu.ruВавиловМ. Н.VavilovM. N.

Аспирант кафедры микробиологии, иммунологии и общей биологии биологического факультета ФГБОУ ВО «Челябинский государственный университет»; биолог лаборатории иммунологических исследований ГБУЗ «Челябинская областная станция переливания крови»

454085, г. Челябинск, ул. Марченко, 7а, кв. 48

Тел.: 8 (952) 508-90-84

Postgraduate Student, Department of Microbiology, Immunology and General Biology, Faculty of Biology, Chelyabinsk State University; Biologist, Laboratory of Immunological Studies, Chelyabinsk Regional Blood Transfusion Station

454085, Chelyabinsk, Marchenko str., 7a, apt 48

Phone: 7 (952) 508-90-84

vavlakhim@mail.ruСташкевичД. С.StashkevichD. S.

К.б.н., доцент, декан биологического факультета

г. Челябинск

PhD (Biology), Associate Professor, Dean, Faculty of Biology

Chelyabinsk

stashkevich_dary@mail.ruСусловаТ. А.SuslovaT. A.

К.м.н., доцент, доцент кафедры микробиологии, иммунологии и общей биологии биологического факультета ФГБОУ ВО «Челябинский государственный университет»; заведующая лабораторией иммунологических исследований ГБУЗ «Челябинская областная станция переливания крови»

г. Челябинск

PhD (Medicine), Associate Professor, Department of Microbiology, Immunology and General Biology, Faculty of Biology, Chelyabinsk State University; Head, Laboratory of Immunological Studies, Chelyabinsk Regional Blood Transfusion Station

Chelyabinsk

tatiana.suslova.hla@gmail.comФГБОУ ВО «Челябинский государственный университет»РоссияChelyabinsk State UniversityRussian FederationФГБОУ ВО «Челябинский государственный университет»; ГБУЗ «Челябинская областная станция переливания крови»РоссияChelyabinsk State University; Chelyabinsk Regional Blood Transfusion StationRussian Federation2022100320222414152Copyright © Бурмистрова А.Л., Вавилов М.Н., Сташкевич Д.С., Суслова Т.А., 20222022Бурмистрова А.Л., Вавилов М.Н., Сташкевич Д.С., Суслова Т.А.Burmistrova A.L., Vavilov M.N., Stashkevich D.S., Suslova T.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2324

Гены MIC расположены на 6-й хромосоме в регионе главного комплекса гистосовместимости (MHC) I класса и кодируют связанный с мембраной стресс-индуцибeльный белок, действующий как лиганд для стимуляции активирующего рецептора, NKG2D, экспрессируемого на поверхности практически всех естественных киллеров человека (NK). На данный момент известно 7 локусов MIC, из которых только MICA и MICB кодируют белковые продукты и обладают существенным аллельным полиморфизмом. Полиморфизм генов MIC и их расположение в регионе HLA на 6-й хромосоме предполагает наличие этнических и межпопуляционных различий в частотах генов, неравновесном сцеплении локусов и в частотах HLA-MIC гаплотипов, что дает возможность получать информацию о генетическом родстве популяций.

Целью нашего исследования является представить иммуногенетический профиль популяции русских Челябинской области на основе неклассических локусов HLA – MICA и MICB, в контексте мировых популяций.

Проведено иммуногенетическое типирование 100 доноров состоящих в Регистре доноров стволовой клетки ГБУЗ «Челябинской областной станции переливания крови», идентифицирующих себя русскими, по 2 локусам MICA и MICB на базовом разрешении, методом полимеразной цепной реакции с сиквенс-специфическими праймерами (SSP-PCR). С помощью программы для иммуногенетических исследований Arlequin 3.5 были рассчитаны частоты генов (GF).

В популяции русских Челябинской области установлены, следующие характеристики профиля генов MICA (MICA*008, *002, *010, *009 с частотой больше 7%; средние частоты MICA*004, *007, *018, *017 и MICA*027, *011, *006, *009:02, *049, *012, *016 с частотой меньше 3,5%), а также профиля генов MICB (MICB*005:02, *004, *002, *008 с частотой больше 6%; с частотой 4% MICB*003, *005:03; MICB*005:01, *005:04, *009N, MICB*013, *014 с частотой 0,5%). На основе расчета генетических расстояний (по Нею) по локусу MICA построена дендрограмма и график рассеяния с использованием метода многомерного шкалирования (MDS), на которых представлено расположение 30 мировых популяций, включая данные по популяции русских Челябинской области. Наименьшие генетические дистанции между популяцией русских Челябинской области и рассмотренными мировыми популя циями обнаружены между жителями Словении, а также населением США европейского происхождения. В результате построения графика рассеяния на основании частот генов MICA методом MDS, с использованием данных кластерного анализа, было установлено, что популяция русских Челябинской области принадлежит к кластеру типичных европейских популяций.

Полученные закономерности могут быть использованы в практической работе для создания регистра доноров стволовых клеток России. Кроме того, данные могут быть использованы как контрольная группа для проведения исследований по направлению «ассоциация HLA с заболеваниями», а также востребованы специалистами по этногенезу в популяционных исследованиях.

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 of

0.5%. 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.

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The authors declare that there are no conflicts of interest present.