期刊
BLOOD
卷 118, 期 19, 页码 5211-5217出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-04-342998
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- University Medical Center Groningen
- Dutch Cancer Society [KWF:RUG2009-4313]
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. (Blood. 2011;118(19):5211-5217)
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