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

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. Meth...

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Autores principales: Fan, Hui-Hui, Guo, Qing, Zheng, Jing, Lian, Yi-Zhi, Huang, Shi-Shi, Sun, Yue, Zou, Ming, Zhu, Jian-Hong, Zhang, Xiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017280/
https://www.ncbi.nlm.nih.gov/pubmed/33815038
http://dx.doi.org/10.3389/fnins.2021.620929
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author Fan, Hui-Hui
Guo, Qing
Zheng, Jing
Lian, Yi-Zhi
Huang, Shi-Shi
Sun, Yue
Zou, Ming
Zhu, Jian-Hong
Zhang, Xiong
author_facet Fan, Hui-Hui
Guo, Qing
Zheng, Jing
Lian, Yi-Zhi
Huang, Shi-Shi
Sun, Yue
Zou, Ming
Zhu, Jian-Hong
Zhang, Xiong
author_sort Fan, Hui-Hui
collection PubMed
description 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.
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spelling pubmed-80172802021-04-03 ALDH1A1 Genetic Variations May Modulate Risk of Parkinson’s Disease in Han Chinese Population Fan, Hui-Hui Guo, Qing Zheng, Jing Lian, Yi-Zhi Huang, Shi-Shi Sun, Yue Zou, Ming Zhu, Jian-Hong Zhang, Xiong Front Neurosci Neuroscience 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. Frontiers Media S.A. 2021-03-19 /pmc/articles/PMC8017280/ /pubmed/33815038 http://dx.doi.org/10.3389/fnins.2021.620929 Text en Copyright © 2021 Fan, Guo, Zheng, Lian, Huang, Sun, Zou, Zhu and Zhang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Fan, Hui-Hui
Guo, Qing
Zheng, Jing
Lian, Yi-Zhi
Huang, Shi-Shi
Sun, Yue
Zou, Ming
Zhu, Jian-Hong
Zhang, Xiong
ALDH1A1 Genetic Variations May Modulate Risk of Parkinson’s Disease in Han Chinese Population
title ALDH1A1 Genetic Variations May Modulate Risk of Parkinson’s Disease in Han Chinese Population
title_full ALDH1A1 Genetic Variations May Modulate Risk of Parkinson’s Disease in Han Chinese Population
title_fullStr ALDH1A1 Genetic Variations May Modulate Risk of Parkinson’s Disease in Han Chinese Population
title_full_unstemmed ALDH1A1 Genetic Variations May Modulate Risk of Parkinson’s Disease in Han Chinese Population
title_short ALDH1A1 Genetic Variations May Modulate Risk of Parkinson’s Disease in Han Chinese Population
title_sort aldh1a1 genetic variations may modulate risk of parkinson’s disease in han chinese population
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017280/
https://www.ncbi.nlm.nih.gov/pubmed/33815038
http://dx.doi.org/10.3389/fnins.2021.620929
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