title: Multiple HLA class I and II associations in classical Hodgkin lymphoma and EBV status defined subgroups.
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.
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Kushi
authors.initials: K
authors.lastname: Kushekhar
authors.forename: Ilja
authors.initials: I
authors.lastname: Nolte
authors.forename: Wierd
authors.initials: W
authors.lastname: Kooistra
authors.forename: Lydia
authors.initials: L
authors.lastname: Visser
authors.forename: Ilby
authors.initials: I
authors.lastname: Bouwman
authors.forename: Niels
authors.initials: N
authors.lastname: Kouprie
authors.forename: Rianne
authors.initials: R
authors.lastname: Veenstra
authors.forename: Gustaaf
authors.initials: G
authors.lastname: van Imhoff
authors.forename: Bianca
authors.initials: B
authors.lastname: Olver
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.forename: Sibrand
authors.initials: S
authors.lastname: Poppema
authors.forename: Arjan
authors.initials: A
authors.lastname: Diepstra
authors.forename: Bouke
authors.initials: B
authors.lastname: Hepkema
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000472:pathogenicity; D006689:Hodgkin Disease / Q000145:classification / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D055815:Young Adult