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Background:  Studies in animal models have suggested that aldehyde dehydrogenase 1 (encoded by  ALDH1A1 ) protects against Parkinson’s disease (PD) by reducing toxic metabolites of dopamine. Herein we aimed to investigate whether  ALDH1A1  was genetically associated with PD susceptibility in humans.   Methods:  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  ALDH1A1  in peripheral blood of 42 subjects.   Results:  The tag-SNP rs7043217 of  ALDH1A1  was significantly associated with PD susceptibility with the T serving as a risk allele (genotype frequency,  P  = 0.030; allele frequency,  P  = 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 ( P  = 9.610 × 10 –8 , 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  ALDH2  variant rs4767944 conferred an elevated protection against PD ( P  = 4.68 × 10 –4 , OR = 0.378, 95% CI = 0.219–0.652). The mRNA expression of  ALDH1A1  showed a trend of reduction ( P  = 0.084) in PD patients compared to the controls.   Conclusion:  Our results provide novel genetic insights into the role of ALDH1 in PD pathogenesis.

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