AUTHOR=He Raoli , Zeng Yuqi , Wang Chaodong , Chen Lina , Cai Guoen , Chen Ying , Wang Yingqing , Ye Qinyong , Chen Xiaochun 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=16

YEAR=2024

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1361492

DOI=10.3389/fnagi.2024.1361492

ISSN=1663-4365

ABSTRACT=<sec id="sec1"><title>Background</title><p>Previous genome-wide association studies investigating the relationship between the <italic>HLA-DRB1</italic> and the risk of Parkinson’s disease (PD) have shown limited racial diversity and have not explored clinical heterogeneity extensively.</p></sec><sec id="sec2"><title>Methods</title><p>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.</p></sec><sec id="sec3"><title>Results</title><p>In the case–control study, <italic>HLA-DRB1</italic> rs660895-G allele was associated with a decreased risk of PD in allele model (adjusted OR=0.72, <italic>p</italic> = 0.003) and dominant model (AG + GG vs. AA: adjusted OR = 0.67, <italic>p</italic> = 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: <italic>β</italic> = −5.42, <italic>p</italic> &lt; 0.001, interaction <italic>p</italic><sub>time × genotype</sub> &lt; 0.001) and non-motor symptoms (NMSS score: <italic>β</italic> = −4.78, <italic>p</italic> = 0.030, interaction <italic>p</italic><sub>time × genotype</sub> &lt; 0.001).</p></sec><sec id="sec4"><title>Conclusion</title><p>Our findings support <italic>HLA-DRB1</italic> 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.</p></sec>