Correlation of Human Leukocyte Antigen-E Genomic Polymorphism with Leukemia and Functional Study of Human Leukocyte Antigen-E Different Type Promoters.

ABSTRACT

Human leukocyte antigen (HLA)-E is one of the least polymorphic nonclassical major histocompatibility complex (MHC) I genes; its nucleotide variability can affect immune response. In this study, we assess the correlation between HLA-E polymorphism and leukemia and further study the transcriptional activity of promoter variation at nucleotide position-26. A total of 142 healthy blood donors and 111 leukemia patients were collected. The genomic sequence of HLA-E was amplified by high-fidelity reaction system and identified by Sanger and cloning sequencing. The dual luciferase reporter gene assay was used to detect the transcription activity of promoter variation at nucleotide position-26. In the HLA-E genomic sequence results, a total of 16 alleles and 32 genotypes were detected; the HLA-E*01010106 allele had a significantly lower frequency in leukemia patients than in healthy participants (p = 0.026 < 0.05). And the HLA-E*01030201, *01030201 genotype showed the greatest difference in frequency between the two groups of participants (p = 0.028 < 0.05). Eight HLA-E alleles were first reported worldwide in Chinese individuals. The results of the dual luciferase reporter gene experiment showed that the transcription activity of the mutant-type promoter (HLA-E*01010106 with "T" allele at nucleotide position-26) was significantly lower compared with the wild-type promoter (HLA-E*01010101 with "G" allele at nucleotide position-26) (p = 0.0242 < 0.05). HLA-E*01010106 allele has a protective effect against leukemia through decreasing transcription activity by "T" variation at nucleotide position-26.