Associative role of HLA-DRB1 as a protective factor for susceptibility and progression of Parkinson's disease: a Chinese cross-sectional and longitudinal study

Raoli He; Yuqi Zeng; Chaodong Wang; Lina Chen; Guoen Cai; Ying Chen; Yingqing Wang; Qinyong Ye; Xiaochun Chen

doi:10.3389/fnagi.2024.1361492

Associative role of HLA-DRB1 as a protective factor for susceptibility and progression of Parkinson's disease: a Chinese cross-sectional and longitudinal study

Front Aging Neurosci. 2024 Feb 22:16:1361492. doi: 10.3389/fnagi.2024.1361492. eCollection 2024.

Authors

Raoli He^#^{1

2

3}, Yuqi Zeng^#^{1

2

3}, Chaodong Wang^#⁴, Lina Chen², Guoen Cai^{1

2

3}, Ying Chen^{1

2

3}, Yingqing Wang^{1

2

3}, Qinyong Ye^{1

2

3}, Xiaochun Chen^{2

3}

Affiliations

¹ Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China.
² Fujian Key Laboratory of Molecular Neurology and Institute of Neuroscience, Fujian Medical University, Fuzhou, China.
³ Institute of Clinical Neurology, Fujian Medical University, Fuzhou, China.
⁴ Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital of Capital Medical University, Beijing, China.

^# Contributed equally.

Abstract

Background: Previous genome-wide association studies investigating the relationship between the HLA-DRB1 and the risk of Parkinson's disease (PD) have shown limited racial diversity and have not explored clinical heterogeneity extensively.

Methods: The study consisted of three parts: a case-control study, a cross-sectional study, and a longitudinal cohort study. The case-control study included 477 PD patients and 477 healthy controls to explore the relationship between rs660895 and PD susceptibility. The cross-sectional study utilized baseline data from 429 PD patients to examine the correlation between rs660895 and PD features. The longitudinal study included 388 PD patients who completed a 3-year follow-up to investigate the effects of rs660895 on PD progression.

Results: In the case-control study, HLA-DRB1 rs660895-G allele was associated with a decreased risk of PD in allele model (adjusted OR=0.72, p = 0.003) and dominant model (AG + GG vs. AA: adjusted OR = 0.67, p = 0.003). In the cross-sectional analysis, there was no association between rs660895 and the onset age, motor phenotype, or initial motor symptoms. In the longitudinal analysis, PD patients with the G allele exhibited a slower progression of motor symptoms (MDS-UPDRS-III total score: β = -5.42, p < 0.001, interaction p_{time × genotype} < 0.001) and non-motor symptoms (NMSS score: β = -4.78, p = 0.030, interaction p_{time × genotype} < 0.001).

Conclusion: Our findings support HLA-DRB1 rs660895-G allele is a protective genetic factor for PD risk in Chinese population. Furthermore, we also provide new evidence for the protective effect of rs660895-G allele in PD progression.

Keywords: HLA-DRB1; Parkinson’s disease; disease progression; disease susceptibility; single nucleotide polymorphism.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from the Project of Industry-university-research Collaborative Innovation in Fujian Province Universities (2022Y4004), the National Natural Science Foundation of China (81870995), the Natural Science Foundation of Fujian Province (2022J01727), and the Key Clinical Specialty Discipline Construction Program of China (21281003).