RESUMEN
Several genes involved in the pathogenesis have been identified, with the human leukocyte antigen (HLA) system playing an essential role. However, the relationship between HLA and a cluster of hematological diseases has received little attention in China. Blood samples (n = 123913) from 43568 patients and 80345 individuals without known pathology were genotyped for HLA class I and II using sequencing-based typing. We discovered that HLA-A*11:01, B*40:01, C*01:02, DQB1*03:01, and DRB1*09:01 were prevalent in China. Furthermore, three high-frequency alleles (DQB1*03:01, DQB1*06:02, and DRB1*15:01) were found to be hazardous in malignant hematologic diseases when compared to controls. In addition, for benign hematologic disorders, 7 high-frequency risk alleles (A*01:01, B*46:01, C*01:02, DQB1*03:03, DQB1*05:02, DRB1*09:01, and DRB1*14:54) and 8 high-frequency susceptible genotypes (A*11:01-A*11:01, B*46:01-B*58:01, B*46:01-B*46:01, C*01:02-C*03:04, DQB1*03:01-DQB1*05:02, DQB1*03:03-DQB1*06:01, DRB1*09:01-DRB1*15:01, and DRB1*14:54-DRB1*15:01) were observed. To summarize, our findings indicate the association between HLA alleles/genotypes and a variety of hematological disorders, which is critical for disease surveillance.
Asunto(s)
Enfermedades Hematológicas , Antígenos de Histocompatibilidad Clase I , Humanos , Frecuencia de los Genes , Alelos , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Genotipo , Antígenos de Histocompatibilidad Clase I/genética , Enfermedades Hematológicas/genética , Haplotipos , Predisposición Genética a la EnfermedadRESUMEN
HLA-A*30:01:24 differs from HLA-A*30:01:01:01 by one nucleotide in exon 3.
Asunto(s)
Pueblos del Este de Asia , Antígenos HLA-A , Humanos , Alelos , Análisis de Secuencia de ADN , Antígenos HLA-A/genética , NucleótidosRESUMEN
HLA-DQB1*06:475 differs from HLA-DQB1*06:35 by one nucleotide in exon 2.
RESUMEN
HLA-A*68:302 differs from HLA-A*68:01:02:01 by one nucleotide in exon 4.
Asunto(s)
Pueblos del Este de Asia , Humanos , Didesoxinucleótidos , Alelos , Análisis de Secuencia de ADNRESUMEN
HLA-C*04:01:152 differs from HLA-C*04:01:01:01 by one nucleotide in exon 1.
Asunto(s)
Pueblos del Este de Asia , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Secuencia de Bases , Nucleótidos , Análisis de Secuencia de ADNRESUMEN
HLA-B*51:381 differs from HLA-B*51:01:01:01 by one nucleotide in exon 5.
Asunto(s)
Antígenos HLA-B , Humanos , Alelos , Pueblos del Este de Asia/genética , Antígenos HLA-B/genética , Nucleótidos , Análisis de Secuencia de ADNRESUMEN
HLA-B*40:536N differs from HLA-B*40:03:01:01 by one nucleotide in exon 3.
Asunto(s)
Pueblos del Este de Asia , Antígenos HLA-B , Humanos , Alelos , Análisis de Secuencia de ADN , Antígenos HLA-B/genética , NucleótidosRESUMEN
The function of natural killer (NK) cells has previously been implicated in hematopoietic-related diseases. Killer immunoglobulin-like receptors (KIR) play an important role in NK cells after hematopoietic stem cell transplantation. To explore the immunogenetic predisposition of hematological-related diseases, herein, a multi-center retrospective study in China was conducted, analyzing and comparing 2519 patients with hematopathy (mainly, acute lymphoblastic leukemia, acute myeloid leukemia, aplastic anemia, and myelodysplastic syndrome) to 18,108 individuals without known pathology. Genotyping was performed by polymerase chain reaction with specific sequence primers (PCR-SSP). As a result, we discovered four genes including KIR2DL5 (OR: 0.74, 95% CI 0.59-0.93; Pc = 0.0405), 2DS1 (OR: 0.74, 95% CI 0.59-0.93; Pc = 0.0405), 2DS3 (OR: 0.58, 95% CI 0.41-0.81; Pc = 0.0180), and 3DS1 (OR: 0.74, 95% CI 0.58-0.94; Pc = 0.0405) to be protective factors that significantly reduce the risk of aplastic anemia. Our findings offer new approaches to immunotherapy for hematological-related diseases. As these therapies mature, they are promising to be used alone or in combination with current treatments to help to make blood disorders a manageable disease.
Asunto(s)
Anemia Aplásica , Enfermedades Hematológicas , Humanos , Estudios Retrospectivos , Anemia Aplásica/genética , Pueblos del Este de Asia , Receptores KIR/genética , Genotipo , Enfermedades Hematológicas/genética , Frecuencia de los GenesRESUMEN
HLA-A*02:07:23 differs from HLA-A*02:07:01:01 by one nucleotide in exon 2.
Asunto(s)
Antígenos HLA-A , Humanos , Alelos , Pueblos del Este de Asia/genética , Antígenos HLA-A/genética , Nucleótidos , Análisis de Secuencia de ADNRESUMEN
HLA-B*44:03:67 differs from HLA-B*44:03:02:01 by one nucleotide in exon 4.
Asunto(s)
Antígenos HLA-B , Humanos , Alelos , Pueblos del Este de Asia/genética , Antígenos HLA-B/genética , Nucleótidos , Análisis de Secuencia de ADNRESUMEN
HLA-DRB1*14:251 differs from HLA-DRB1*14:126:01 by one nucleotide in exon 2.
Asunto(s)
Pueblos del Este de Asia , Nucleótidos , Humanos , Cadenas HLA-DRB1/genética , Alelos , Secuencia de Bases , Análisis de Secuencia de ADNRESUMEN
HLA-C*12:368 differs from HLA-C*12:03:01:01 by one nucleotide in exon 4.
Asunto(s)
Pueblos del Este de Asia , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Secuencia de Bases , Nucleótidos , Análisis de Secuencia de ADNRESUMEN
HLA-C*03:621 differs from HLA-C*03:04:01:01 by one nucleotide in exon 1.
Asunto(s)
Pueblos del Este de Asia , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Secuencia de Bases , Nucleótidos , Análisis de Secuencia de ADNRESUMEN
HLA-DPB1*05:01:18 differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 4.
Asunto(s)
Pueblos del Este de Asia , Nucleótidos , Humanos , Alelos , Análisis de Secuencia de ADNRESUMEN
HLA-B*13:176 differs from HLA-B*13:02:01:01 by one nucleotide in exon 1.
Asunto(s)
Pueblos del Este de Asia , Antígenos HLA-B , Antígeno HLA-B13 , Humanos , Alelos , Antígenos HLA-B/genética , Nucleótidos , Análisis de Secuencia de ADN , Antígeno HLA-B13/genéticaRESUMEN
HLA-C*01:02:89 differs from HLA-C*01:02:01:01 by one nucleotide in exon 2.
Asunto(s)
Pueblos del Este de Asia , Antígenos HLA-C , Humanos , Alelos , Antígenos HLA-C/genética , Análisis de Secuencia de ADNRESUMEN
HLA-B*55:131 differs from HLA-B*55:02:01:01 by one nucleotide in exon 4.
Asunto(s)
Antígenos HLA-B , Humanos , Alelos , Pueblos del Este de Asia , Antígenos HLA-B/genética , Nucleótidos , Análisis de Secuencia de ADNRESUMEN
HLA-B*15:644 differs from HLA-B*15:17:01:02 by one nucleotide in exon 4.
Asunto(s)
Antígenos HLA-B , Humanos , Alelos , Pueblos del Este de Asia , Antígenos HLA-B/genética , Nucleótidos , Análisis de Secuencia de ADNRESUMEN
HLA-DQB1*02:01:44 differs from HLA-DQB1*02:01:01:01 by one nucleotide in exon 2.
Asunto(s)
Cadenas beta de HLA-DQ , Humanos , Alelos , Secuencia de Bases , Pueblos del Este de Asia , Cadenas beta de HLA-DQ/genética , NucleótidosRESUMEN
HLA-DRB1*14:07:03 differs from HLA-DRB1*14:07:01 by one nucleotide in exon 2.