NGS identifies novel HLA-DQA1 and DPB1 associations with aplastic anemia in the Kazakhstani population

Turganbekova A. Zhanzakova Z. Kanabekova P. Baimukasheva D. Saduakas Z. Khamitova D. Abdrakhmanova S. Masalimov Z. Almawi W.Y.
2026 Frontiers Media SA

Frontiers in Immunology
2026 #17

Background: 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. Objective: 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. Methods: 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. Results: Class II alleles showed stronger associations with AA than Class I alleles. Novel HLA associations with strong effect sizes (ORs >69) were identified, including the first-ever reported associations between HLA-DQA1 alleles and AA susceptibility. DRB1*05:05:01, DRB1*01:02:01, DQA1*05:05:01, DQA1*03:03:01, DQA1*03:02:01, DQA1*01:04:01, DQB1*02:02:01, DPB1*02:01:02, and DPB1*104:01:01 were associated with a higher AA risk in the Kazakhstani population. In contrast, DRB1*07:01:01, DRB1*15:01:01, DQA1*03:01:01, DQA1*01:01:01, DQA1*05:01:01, DQB1*02:01:01, and DPB1*02:01:01 were linked with reduced risk. Among Class I alleles, only B*40:02:01 showed a weak association with increased AA risk (p = 0.042), markedly lower than the strong Class II effects. Conclusions: Class II alleles, including those within DQA1 and DPB1, 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. Copyright

aplastic anemia , DPB1 alleles , DQA1 alleles , HLA polymorphisms , next-generation sequencing

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HLA Laboratory, Scientific and Production Center for Transfusiology, Astana, Kazakhstan
Faculty of Natural Sciences, L.N. Gumilyov Eurasian National University, Astana, Kazakhstan
School of Medicine, Nazarbayev University, Astana, Kazakhstan
Faculty of Sciences, El-Manar University, Tunis, Tunisia

HLA Laboratory
Faculty of Natural Sciences
School of Medicine
Faculty of Sciences

10 лет помогаем публиковать статьи Международный издатель

Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026