title: HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV+ Hodgkin lymphoma.
abstract: Previous studies showed that the HLA class I region is associated with Epstein-Barr virus (EBV)-positive Hodgkin lymphoma (HL) and that HLA-A is the most likely candidate gene in this region. This suggests that antigenic presentation of EBV-derived peptides in the context of HLA-A is involved in the pathogenesis of EBV+ HL by precluding efficient immune responses. We genotyped exons 2 and 3, encoding the peptide-binding groove of HLA-A, for 32 single nucleotide polymorphisms in 70 patients with EBV+ HL, 31 patients with EBV- HL, and 59 control participants. HLA-A*01 was significantly overrepresented and HLA-A*02 was significantly underrepresented in patients with EBV+ HL versus controls and patients with EBV- HL. In addition, HLA-A*02 status was determined by immunohistochemistry or HLA-A*02-specific polymerase chain reaction (PCR) on 152 patients with EBV+ HL and 322 patients with EBV- HL. The percentage of HLA-A*02+ patients in the EBV+ HL group (35.5%) was significantly lower than in 6107 general control participants (53.0%) and the EBV- HL group (50.9%). Our results indicate that individuals carrying the HLA-A*02 allele have a reduced risk of developing EBV+ HL, while individuals carrying the HLA-A*01 allele have an increased risk. It is known that HLA-A*02 can present EBV-derived peptides and can evoke an effective immune response, which may explain the protective phenotype.
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
authors.forename: Marijke
authors.initials: M
authors.lastname: Niens
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Jarrett
authors.forename: Bouke
authors.initials: B
authors.lastname: Hepkema
authors.forename: Ilja M
authors.initials: IM
authors.lastname: Nolte
authors.forename: Arjan
authors.initials: A
authors.lastname: Diepstra
authors.forename: Mathieu
authors.initials: M
authors.lastname: Platteel
authors.forename: Niels
authors.initials: N
authors.lastname: Kouprie
authors.forename: Craig P
authors.initials: CP
authors.lastname: Delury
authors.forename: Alice
authors.initials: A
authors.lastname: Gallagher
authors.forename: Lydia
authors.initials: L
authors.lastname: Visser
authors.forename: Sibrand
authors.initials: S
authors.lastname: Poppema
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: te Meerman
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D015234:HLA-A Antigens / Q000235:genetics*; D015788:HLA-A1 Antigen; D015789:HLA-A2 Antigen; D006239:Haplotypes; D006689:Hodgkin Disease / Q000150:complications / Q000235:genetics* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D015234:HLA-A Antigens; C524866:HLA-A*02 antigen; D015788:HLA-A1 Antigen; D015789:HLA-A2 Antigen