Frontiers in immunology · 2026
NGS identifies novel HLA-DQA1 and DPB1 associations with aplastic anemia in the Kazakhstani population.
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Turganbekova Aida, Zhanzakova Zhulduz, Kanabekova Perizat, Baimukasheva Dana, Saduakas Zhazira, Khamitova Didara, Abdrakhmanova Saniya, Masalimov Zhaksylyk, Almawi Wassim Y
Аннотация
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.
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.