AUTHOR=Fan Hui-Hui , Guo Qing , Zheng Jing , Lian Yi-Zhi , Huang Shi-Shi , Sun Yue , Zou Ming , Zhu Jian-Hong , Zhang Xiong 

TITLE=ALDH1A1 Genetic Variations May Modulate Risk of Parkinson’s Disease in Han Chinese Population

JOURNAL=Frontiers in Neuroscience

VOLUME=15

YEAR=2021

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.620929

DOI=10.3389/fnins.2021.620929

ISSN=1662-453X

ABSTRACT=<p><bold>Background:</bold> Studies in animal models have suggested that aldehyde dehydrogenase 1 (encoded by <italic>ALDH1A1</italic>) protects against Parkinson’s disease (PD) by reducing toxic metabolites of dopamine. Herein we aimed to investigate whether <italic>ALDH1A1</italic> was genetically associated with PD susceptibility in humans.</p><p><bold>Methods:</bold> A Han Chinese population of 1,039 subjects was recruited to analyze six tag-single nucleotide polymorphisms (SNPs), followed by haplotype analyses and variants interaction analyses. Real-time PCR was used to analyze mRNA levels of <italic>ALDH1A1</italic> in peripheral blood of 42 subjects.</p><p><bold>Results:</bold> The tag-SNP rs7043217 of <italic>ALDH1A1</italic> was significantly associated with PD susceptibility with the T serving as a risk allele (genotype frequency, <italic>P</italic> = 0.030; allele frequency, <italic>P</italic> = 0.013, OR = 1.258, 95% CI = 1.050–1.508). Multiple haplotypes were linked to abnormalities of PD risk, topped by a 4-SNP GGTA module in the order of rs4646547, rs1888202, rs7043217, and rs647880 (<italic>P</italic> = 9.610 × 10<sup>–8</sup>, OR = 6.420, 95% CI = 2.944–13.998). Interaction analyses showed that a simultaneous presence of the CC genotype of rs7043217 and the TT genotype of <italic>ALDH2</italic> variant rs4767944 conferred an elevated protection against PD (<italic>P</italic> = 4.68 × 10<sup>–4</sup>, OR = 0.378, 95% CI = 0.219–0.652). The mRNA expression of <italic>ALDH1A1</italic> showed a trend of reduction (<italic>P</italic> = 0.084) in PD patients compared to the controls.</p><p><bold>Conclusion:</bold> Our results provide novel genetic insights into the role of ALDH1 in PD pathogenesis.</p>