title: Common Genetic Variant Association with Altered HLA Expression, Synergy with Pyrethroid Exposure, and Risk for Parkinson's Disease: An Observational and Case-Control Study.
abstract: OBJECTIVE
  The common non-coding single nucleotide polymorphism (SNP)rs3129882inHLA-DRAis associated with risk for idiopathic Parkinson's disease (PD). The location of the SNP in the major histocompatibility complex class II (MHC-II) locus implicates regulation of antigen presentation as a potential mechanism by which immune responses link genetic susceptibility to environmental factors in conferring lifetime risk for PD.
  
  
  METHODS
  For immunophenotyping, blood cells from 81 subjects were analyzed by qRT-PCR and flow cytometry. A case-control study was performed on a separate cohort of 962 subjects to determine association of pesticide exposure and the SNP with risk of PD.
  
  
  RESULTS
  Homozygosity forGat this SNP was associated with heightened baseline expression and inducibility of MHC class II molecules in B cells and monocytes from peripheral blood of healthy controls and PD patients. In addition, exposure to a commonly used class of insecticide, pyrethroids, synergized with the risk conferred by this SNP (OR = 2.48, p = 0.007), thereby identifying a novel gene-environment interaction that promotes risk for PD via alterations in immune responses.
  
  
  CONCLUSIONS
  In sum, these novel findings suggest that the MHC-II locus may increase susceptibility to PD through presentation of pathogenic, immunodominant antigens and/or a shift toward a more pro-inflammatory CD4+ T cell response in response to specific environmental exposures, such as pyrethroid exposure through genetic or epigenetic mechanisms that modulate MHC-II gene expression.
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: G T
authors.initials: GT
authors.lastname: Kannarkat
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: D A
authors.initials: DA
authors.lastname: Cook
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: J-K
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: J
authors.initials: J
authors.lastname: Chung
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: E
authors.initials: E
authors.lastname: Sandy
authors.affiliation: Department of Epidemiology and Center for Occupational and Environmental Health, Fielding School of Public Health, University of California at Los Angeles, Los Angeles, CA.
authors.forename: K C
authors.initials: KC
authors.lastname: Paul
authors.affiliation: Department of Epidemiology and Center for Occupational and Environmental Health, Fielding School of Public Health, University of California at Los Angeles, Los Angeles, CA.
authors.forename: B
authors.initials: B
authors.lastname: Ritz
authors.affiliation: Department of Neurology, School of Medicine, University of California at Los Angeles, Los Angeles, CA.
authors.forename: J
authors.initials: J
authors.lastname: Bronstein
authors.affiliation: Department of Neurology and Movement Disorders Center, Emory University School of Medicine, Atlanta, GA.
authors.forename: S A
authors.initials: SA
authors.lastname: Factor
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA.
authors.forename: J M
authors.initials: JM
authors.lastname: Boss
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: M G
authors.initials: MG
authors.lastname: Tansey