BACKGROUND/OBJECTIVES The common non-coding single nucleotide polymorphism (SNP) rs3129882 in HLA-DRA is 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 for G at 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.

中文翻译：

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常见的遗传变异与HLA表达改变，与拟除虫菊酯暴露的协同作用以及帕金森氏病风险的关联：一项观察和病例对照研究。

背景/目的HLA-DRA中常见的非编码单核苷酸多态性（SNP）rs3129882与特发性帕金森氏病（PD）的风险有关。SNP在主要组织相容性复合体II类（MHC-II）基因座中的位置暗示了抗原呈递的调节，这是一种潜在的机制，通过该机制免疫反应将遗传易感性与环境因素联系在一起，从而延长了PD的终生风险。方法为进行免疫表型分析，通过qRT-PCR和流式细胞仪分析了81名受试者的血细胞。对另外962名受试者进行了病例对照研究，以确定农药暴露和SNP与PD风险的相关性。结果该SNP的G纯合性与健康对照组和PD患者外周血B细胞和单核细胞中基线表达的增强和MHC II类分子的诱导性有关。此外，暴露于一种常用的杀虫剂拟除虫菊酯中，与该SNP所带来的风险协同作用（OR = 2.48，p = 0.007），从而确定了一种新型的基因-环境相互作用，该相互作用通过改变免疫应答而提高了PD的风险。 。结论总而言之，这些新发现表明，MHC-II基因座可通过呈递致病性，免疫显性抗原和/或响应特定的环境暴露而转向更具促炎性的CD4 + T细胞应答，从而增加对PD的易感性，