title: The evolving story of human leukocyte antigen and the immunogenetics of peanut allergy.
abstract: OBJECTIVE
  Peanut allergy (PA) clearly has a heritable component. Specific genetic contributions are unknown, but human leukocyte antigen (HLA) loci are obvious candidates. This review focuses on emerging studies of HLA associations with PA.
  
  
  METHODS
  PubMed was searched with no time limitations using key terms human leukocyte antigen, HLA, MHC, peanut, peanut hypersensitivity, and peanut allergy.
  
  
  METHODS
  Qualifying studies were English-language reports of genetic analyses examining PA and HLA associations.
  
  
  RESULTS
  Seven relevant citations were identified, which were published from 1996 to 2015. Early studies using candidate gene approaches found associations between PA and HLA-DR and -DQ alleles (HLA-DRB1*08 and DQB1*06:03P) when comparing subjects with peanut allergy with nonallergic unrelated control groups. No significant associations were found between siblings with and without peanut allergy. However, a recent large genomewide association study of patients with peanut allergy and their family members found 2 PA-associated single-nucleotide polymorphisms (rs9275596 and rs7192) mapping to regions involving the HLA-DR and HLA-DQ genes. Associations with differential DNA methylation partly mediated the associations between PA and single-nucleotide polymorphisms.
  
  
  CONCLUSIONS
  Early studies using candidate gene approaches identified HLA associations with PA compared with the general population, suggesting a link with atopy but failing to identify a PA-specific association. These studies had various limitations that included small samples. The most compelling evidence for a PA-specific HLA association comes from a genomewide association study, which examined the entire genome in large, well-defined, related cohorts. More research is needed to validate and replicate these findings, to perform fine genetic mapping of specific HLA loci, and to demonstrate underlying mechanisms of HLA contributions to PA.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Hemler
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Pharmacology, Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, Nashville, Tennessee; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Phillips
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; Center for Translational Immunology and Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Mallal
authors.affiliation: Division of Allergy, Pulmonary and Critical Care, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee. Electronic address: peggy.kendall@vanderbilt.edu.
authors.forename: Peggy L
authors.initials: PL
authors.lastname: Kendall
mesh_terms: D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D021183:Peanut Hypersensitivity / Q000235:genetics* / Q000276:immunology
chemical_list: D006680:HLA Antigens