Human Leukocyte Antigen in Parkinson’S Disease: A Systematic Review and Meta-Analysis of Risk and Clinical Attributes Publisher Pubmed



Salari M ; Rezaei K ; Eini P ; Alikhani A ; Etemadifar M
Source: Neurological Sciences Published:2025

Abstract

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder potentially influenced by immune system dysregulation, with the human leukocyte antigen (HLA) system implicated in its pathogenesis. This study aims to evaluate HLA variants’ association with PD risk and clinical attributes. Methods: A systematic review and meta-analysis, registered with PROSPERO (CRD420250650550) and adhering to PRISMA Guidelines, was conducted. PubMed, Web of Science, and Scopus were searched from February 2005 to February 2025 for determined keywords. Eligible studies included human-based primary research reporting HLA associations with PD risk or clinical features. Data was extracted on study characteristics, HLA alleles/genotypes, and clinical outcomes. Meta-analysis used fixed-effect models to pool odds ratios (ORs) with 95% confidence intervals (CIs), assessing heterogeneity via I2 and Cochran’s Q statistics. Publication bias was evaluated using the trim-and-fill method. Results: Sixteen studies analyzing 42 HLA markers were included. Pooled ORs indicated increased PD risk with insignificant heterogeneity for HLA-B*07, HLA-C*07:02, HLA-DQA1*01:02, HLA-DQA1*05:05, HLA-DRB1*03:01, and HLA-DRB1*15:01, with protective effects for HLA-DQB1*03:02 and HLA-DQB1*04:01. The analysis for HLA genotypes showed substantial heterogeneity across the studies. The publication bias effect was limited using trim-and-fill method, affecting all the homogenous analyses. HLA-DR expression correlated with motor-cognitive function, and HLA-DQB1*06:02 was linked to daytime sleepiness. Conclusion: Specific HLA alleles influence PD susceptibility and clinical presentation, highlighting the immune system’s role in PD pathogenesis. Future research may explore the influence of HLA haplotypes on PD to ascertain whether there is a direct impact or if the associations are merely a consequence of linkage disequilibrium. © 2025 Elsevier B.V., All rights reserved.