Investigation of HLA susceptibility alleles and genotypes with hematological disease among Chinese Han population.

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.

The novel HLA-DQB1*06:475 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DQB1*06:475 differs from HLA-DQB1*06:35 by one nucleotide in exon 2.

The novel HLA-A*30:01:24 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-A*30:01:24 differs from HLA-A*30:01:01:01 by one nucleotide in exon 3.

The novel HLA-C*04:01:152 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*04:01:152 differs from HLA-C*04:01:01:01 by one nucleotide in exon 1.

The novel HLA-A*68:302 allele, identified by Sanger dideoxynucleotide sequencing in a Chinese individual.

HLA-A*68:302 differs from HLA-A*68:01:02:01 by one nucleotide in exon 4.

Exploration of KIR genes and hematological-related diseases in Chinese Han population.

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.

The novel HLA-B*51:381 allele, identified in a Chinese individual through Sanger dideoxy nucleotide sequencing.

HLA-B*51:381 differs from HLA-B*51:01:01:01 by one nucleotide in exon 5.

The novel HLA-B*40:536N allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*40:536N differs from HLA-B*40:03:01:01 by one nucleotide in exon 3.

The novel HLA-B*44:03:67 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*44:03:67 differs from HLA-B*44:03:02:01 by one nucleotide in exon 4.

The novel HLA-A*02:07:23 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-A*02:07:23 differs from HLA-A*02:07:01:01 by one nucleotide in exon 2.

The novel HLA-DRB1*14:251 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DRB1*14:251 differs from HLA-DRB1*14:126:01 by one nucleotide in exon 2.

The novel HLA-C*12:368 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*12:368 differs from HLA-C*12:03:01:01 by one nucleotide in exon 4.

The novel HLA-DPB1*05:01:18 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DPB1*05:01:18 differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 4.

The novel HLA-C*03:621 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*03:621 differs from HLA-C*03:04:01:01 by one nucleotide in exon 1.

The novel HLA-B*13:176 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*13:176 differs from HLA-B*13:02:01:01 by one nucleotide in exon 1.

The novel HLA-DQB1*03:03:29 allele, identified by sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DQB1*03:03:29 differs from HLA-DQB1*03:03:02:01 by one nucleotide in exon 2.

The novel HLA-C*15:02:58 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*15:02:58 differs from HLA-C*15:02:01:01 by one nucleotide in exon 1.

The novel HLA-A*02:1075 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-A*02:1075 differs from HLA-A*02:07:01:01 by one nucleotide in exon 5.

The novel HLA-C*07:1029 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*07:1029 differs from HLA-C*07:02:01:01 by one nucleotide in exon 5.

The novel HLA-B*35:568 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*35:568 differs from HLA-B*35:03:01:01 by one nucleotide in exon 4.