ABSTRACT
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.
Subject(s)
Hematologic Diseases , Histocompatibility Antigens Class I , Humans , Gene Frequency , Alleles , HLA-DQ beta-Chains/genetics , HLA-DRB1 Chains/genetics , Genotype , Histocompatibility Antigens Class I/genetics , Hematologic Diseases/genetics , Haplotypes , Genetic Predisposition to DiseaseABSTRACT
HLA-A*30:01:24 differs from HLA-A*30:01:01:01 by one nucleotide in exon 3.
Subject(s)
East Asian People , HLA-A Antigens , Humans , Alleles , Sequence Analysis, DNA , HLA-A Antigens/genetics , NucleotidesABSTRACT
HLA-DQB1*06:475 differs from HLA-DQB1*06:35 by one nucleotide in exon 2.
ABSTRACT
HLA-A*68:302 differs from HLA-A*68:01:02:01 by one nucleotide in exon 4.
Subject(s)
East Asian People , Humans , Dideoxynucleotides , Alleles , Sequence Analysis, DNAABSTRACT
HLA-C*04:01:152 differs from HLA-C*04:01:01:01 by one nucleotide in exon 1.
Subject(s)
East Asian People , HLA-C Antigens , Humans , HLA-C Antigens/genetics , Alleles , Base Sequence , Nucleotides , Sequence Analysis, DNAABSTRACT
HLA-B*51:381 differs from HLA-B*51:01:01:01 by one nucleotide in exon 5.
Subject(s)
HLA-B Antigens , Humans , Alleles , East Asian People/genetics , HLA-B Antigens/genetics , Nucleotides , Sequence Analysis, DNAABSTRACT
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.
Subject(s)
Anemia, Aplastic , Hematologic Diseases , Humans , Retrospective Studies , Anemia, Aplastic/genetics , East Asian People , Receptors, KIR/genetics , Genotype , Hematologic Diseases/genetics , Gene FrequencyABSTRACT
HLA-B*40:536N differs from HLA-B*40:03:01:01 by one nucleotide in exon 3.
Subject(s)
East Asian People , HLA-B Antigens , Humans , Alleles , Sequence Analysis, DNA , HLA-B Antigens/genetics , NucleotidesABSTRACT
HLA-A*02:07:23 differs from HLA-A*02:07:01:01 by one nucleotide in exon 2.
Subject(s)
HLA-A Antigens , Humans , Alleles , East Asian People/genetics , HLA-A Antigens/genetics , Nucleotides , Sequence Analysis, DNAABSTRACT
HLA-B*44:03:67 differs from HLA-B*44:03:02:01 by one nucleotide in exon 4.
Subject(s)
HLA-B Antigens , Humans , Alleles , East Asian People/genetics , HLA-B Antigens/genetics , Nucleotides , Sequence Analysis, DNAABSTRACT
HLA-C*12:368 differs from HLA-C*12:03:01:01 by one nucleotide in exon 4.
Subject(s)
East Asian People , HLA-C Antigens , Humans , HLA-C Antigens/genetics , Alleles , Base Sequence , Nucleotides , Sequence Analysis, DNAABSTRACT
HLA-DRB1*14:251 differs from HLA-DRB1*14:126:01 by one nucleotide in exon 2.
Subject(s)
East Asian People , Nucleotides , Humans , HLA-DRB1 Chains/genetics , Alleles , Base Sequence , Sequence Analysis, DNAABSTRACT
HLA-C*03:621 differs from HLA-C*03:04:01:01 by one nucleotide in exon 1.
Subject(s)
East Asian People , HLA-C Antigens , Humans , HLA-C Antigens/genetics , Alleles , Base Sequence , Nucleotides , Sequence Analysis, DNAABSTRACT
HLA-DPB1*05:01:18 differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 4.
Subject(s)
East Asian People , Nucleotides , Humans , Alleles , Sequence Analysis, DNAABSTRACT
HLA-B*13:176 differs from HLA-B*13:02:01:01 by one nucleotide in exon 1.
Subject(s)
East Asian People , HLA-B Antigens , HLA-B13 Antigen , Humans , Alleles , HLA-B Antigens/genetics , Nucleotides , Sequence Analysis, DNA , HLA-B13 Antigen/geneticsABSTRACT
HLA-DQB1*03:03:29 differs from HLA-DQB1*03:03:02:01 by one nucleotide in exon 2.
Subject(s)
HLA-DQ beta-Chains , Humans , Alleles , Base Sequence , East Asian People , HLA-DQ beta-Chains/genetics , NucleotidesABSTRACT
HLA-C*01:02:89 differs from HLA-C*01:02:01:01 by one nucleotide in exon 2.
Subject(s)
East Asian People , HLA-C Antigens , Humans , Alleles , HLA-C Antigens/genetics , Sequence Analysis, DNAABSTRACT
HLA-B*15:644 differs from HLA-B*15:17:01:02 by one nucleotide in exon 4.
Subject(s)
HLA-B Antigens , Humans , Alleles , East Asian People , HLA-B Antigens/genetics , Nucleotides , Sequence Analysis, DNAABSTRACT
HLA-DQB1*04:93 differs from HLA-DQB1*04:01:01:01 by one nucleotide in exon 2.
Subject(s)
HLA-DQ beta-Chains , Humans , Alleles , Base Sequence , East Asian People , HLA-DQ beta-Chains/genetics , NucleotidesABSTRACT
HLA-DQB1*02:01:44 differs from HLA-DQB1*02:01:01:01 by one nucleotide in exon 2.