1. Multiple HLA class I and II associations in classical Hodgkin lymphoma and EBV status defined subgroups.
- Author
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Huang X, Kushekhar K, Nolte I, Kooistra W, Visser L, Bouwman I, Kouprie N, Veenstra R, van Imhoff G, Olver B, Houlston RS, Poppema S, Diepstra A, Hepkema B, and van den Berg A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Epstein-Barr Virus Infections genetics, Epstein-Barr Virus Infections immunology, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Herpesvirus 4, Human isolation & purification, Herpesvirus 4, Human pathogenicity, Hodgkin Disease classification, Hodgkin Disease virology, Humans, Linkage Disequilibrium, Male, Middle Aged, Netherlands, Young Adult, Genes, MHC Class I, Genes, MHC Class II, Hodgkin Disease genetics, Hodgkin Disease immunology
- Abstract
The pathogenesis of classical Hodgkin lymphoma (cHL) involves environmental and genetic factors. To explore the role of the human leukocyte antigen (HLA) genes, we performed a case-control genotyping study in 338 Dutch cHL patients and more than 5000 controls using a PCR-based sequence-specific oligonucleotide probe hybridization approach. HLA-A68 and HLA-DR11 (5) were significantly increased in the cHL patient population compared with the controls. Three class II associations were observed in the EBV(-) cHL population with an increase of HLA-DR15 (2) and a decrease of HLA-DR4 and HLA-DR7. Allele frequencies of HLA-A1, HLA-B37, and HLA-DR10 were significantly increased in the EBV(+) cHL population; these alleles are in strong linkage disequilibrium and form a common haplotype in whites. The allele frequency of HLA-A2 was significantly decreased in the EBV(+) cHL population. Sequence-specific oligonucleotide probe analysis revealed significant differences between EBV(+) and EBV(-) cHL patients for 19 probes that discriminate between HLA-A*01 and HLA-A*02. In conclusion, the HLA-A1 and HLA-A2 antigens and not specific single nucleotide variants shared by multiple alleles are responsible for the association with EBV(+) cHL. Furthermore, several new protective and predisposing HLA class I and II associations for the EBV(+), the EBV(-), and the entire cHL population were identified.
- Published
- 2011
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