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Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterised by a high prevalence of sporadic cases. Various molecular mechanisms are involved in its pathogenesis. This pilot study aimed to identify potential risk and protective human leukocyte antigen (HLA) alleles in PD, discover candidate alleles for further research, and evaluate potential blood biomarkers. Methods: A total of 43 PD patients and 79 unrelated sex-matched controls were enrolled in this study. We analysed the polymorphism of HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles and the blood levels of biomarkers such as S100 calcium-binding protein A9 (S1000A9), kynurenic acid (KYNA), neurofilament light chain (NfL), and glutamate decarboxylase (GAD1). Results: We found that the frequencies of the HLA-DRB1*04, -DQA1*02:01, and -DQA1*03:01 alleles were significantly higher in the PD patients than in the controls, suggesting that these alleles are potential risk factors. Furthermore, the HLA-DQA1*02:01 allele was detected more frequently in the PD group when the disease onset was at 60 years or older. On the contrary, the HLA-DRB1*01 and HLA-DQA1*05:01 alleles were less common in the PD patients, indicating a possible protective effect. Regarding biomarkers, the blood levels of S100 calcium-binding protein A9 were significantly higher, and the kynurenic acid levels were significantly lower in the PD group. The NfL levels were also higher in the PD group but did not reach statistical significance, possibly due to the sensitivity limitations of the ELISA method used. The GAD1 levels showed no significant differences between the two groups. Conclusions: Our findings indicate that the HLA-DRB1*01 and -DRB1*04 alleles and the HLA-DQA1*02:01, -DQA1*03:01, and -DQA1*05:01 alleles are associated with PD. Moreover, S100 calcium-binding protein A9 and kynurenic acid can be considered potential blood biomarkers for PD. These findings contribute to the growing body of knowledge on PD and offer new directions for further research in Latvian cohorts.