{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T13:42:09Z","timestamp":1782135729419,"version":"3.54.5"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n Aplastic anemia (AA) is a rare but serious blood disorder defined by autoimmune-driven destruction of bone marrow stem and progenitor cells. HLA polymorphisms are AA risk factors, with population-specific associations influencing disease susceptibility, treatment response, and transplant outcomes. While the genetic pathways driving AA development remain incompletely elucidated, a link between HLA variants and AA predisposition has been documented across diverse ethnic groups, though not in Central Asian communities, particularly in Kazakhstan.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n We investigated the relationship between HLA Class I and Class II alleles and the risk of AA in the Kazakhstani population using high-resolution NGS genotyping.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n The study included 91 patients with AA and 250 unrelated controls selected from the national registry of hematopoietic stem cell donors. HLA class I (A\/C\/B) and class II (DRB1\/DQA1\/DQB1\/DPB1) high-resolution genotyping was conducted using NGS. Statistical significance was assessed with chi-square tests.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Class II alleles showed stronger associations with AA than Class I alleles. Novel HLA associations with strong effect sizes (ORs &gt;69) were identified, including the first-ever reported associations between\n HLA-DQA1<\/jats:italic>\n alleles and AA susceptibility.\n DRB1*05:05:01<\/jats:italic>\n ,\n DRB1*01:02:01<\/jats:italic>\n ,\n DQA1*05:05:01<\/jats:italic>\n ,\n DQA1*03:03:01<\/jats:italic>\n ,\n DQA1*03:02:01<\/jats:italic>\n ,\n DQA1*01:04:01<\/jats:italic>\n ,\n DQB1*02:02:01<\/jats:italic>\n ,\n DPB1*02:01:02<\/jats:italic>\n , and\n DPB1<\/jats:italic>\n *\n 104:01:01<\/jats:italic>\n were associated with a higher AA risk in the Kazakhstani population. In contrast,\n DRB1*07:01:01<\/jats:italic>\n ,\n DRB1*15:01:01<\/jats:italic>\n ,\n DQA1*03:01:01<\/jats:italic>\n ,\n DQA1*01:01:01<\/jats:italic>\n ,\n DQA1*05:01:01<\/jats:italic>\n ,\n DQB1*02:01:01<\/jats:italic>\n , and\n DPB1*02:01:01<\/jats:italic>\n were linked with reduced risk. Among Class I alleles, only\n B*40:02:01<\/jats:italic>\n showed a weak association with increased AA risk (\n p<\/jats:italic>\n = 0.042), markedly lower than the strong Class II effects.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Class II alleles, including those within\n DQA1<\/jats:italic>\n and\n DPB1<\/jats:italic>\n , are important genetic factors influencing AA susceptibility in Kazakhstan. It highlights the need for region-specific genetic profiling to improve disease risk assessment and guide therapeutic strategies.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1752687","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T06:45:48Z","timestamp":1770273948000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["NGS identifies novel HLA-DQA1 and DPB1 associations with aplastic anemia in the Kazakhstani population"],"prefix":"10.3389","volume":"17","author":[{"given":"Aida","family":"Turganbekova","sequence":"first","affiliation":[{"name":"HLA Laboratory, Scientific and Production Center for Transfusiology","place":["Astana, Kazakhstan"]},{"name":"Faculty of Natural Sciences, L.N. 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