Parkinson’s disease (PD; Online Mendelian Inheritance in Man: 168600) is one of the most common neurodegenerative diseases with its characteristic motor symptoms described as parkinsonism and nonmotor symptoms. The core pathology is the progressive loss of dopaminergic neurons in the substantia nigra with deposition of protein aggregates containing α-synuclein.1 Aberrant functioning of the immune system in the nervous system has been proposed as a critical contributor to the pathogenesis of PD.2 Consistently, some of genetic loci identified by genome-wide association studies (GWAS) are related to immune function.3-6 Among them, the human leukocyte antigen (HLA) genes in the major histocompatibility complex (MHC; 6p21.3) have been implicated in the pathogenesis of PD.7, 8 For example, HLA molecules bind to α-synuclein and trigger T cell activation, and its reactivities might depend on the variations in HLA alleles.7 Thus, the elucidation of the risk-associated HLA variants should contribute to further understanding of its pathogenesis.
The association of a variant in the HLA region with PD was first reported in 2010, which was a noncoding variant influencing the expression of HLA-DR and HLA-DQ.9 Since then, different studies have reported the associations in various aspects, including haplotypes and regulatory variants,10 single nucleotide polymorphisms (SNPs) along with smoking history,10 and specific combinations of amino acid polymorphisms in HLA-DRB1.
Reference link- https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28583
