ALDH1A1 Genetic Variations May Modulate Risk of Parkinson's Disease in Han Chinese Population.
ALDH1A1 Genetic Variations May Modulate Risk of Parkinson's Disease in Han Chinese Population.
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ALDH1A1 基因变异可能会调节中国汉族人群患帕金森病的风险
DOI：
10.3389/fnins.2021.620929
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发表时间：
2021
影响因子：
4.3
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Fan HH;Guo Q;Zheng J;Lian YZ;Huang SS;Sun Y;Zou M;Zhu JH;Zhang X
背景资料：在动物模型中的研究表明，醛脱氢酶1（由ALDH 1A 1编码）通过减少多巴胺的有毒代谢物来预防帕金森病（PD）。在此，我们的目的是调查ALDH 1A 1是否与人类PD易感性遗传相关。研究方法：招募了1,039名中国汉族受试者，分析了6个标签-单核苷酸多态性（SNP），随后进行单倍型分析和变体相互作用分析。采用Real-time PCR检测42例受试者外周血ALDH 1A 1 mRNA水平。结果如下：ALDH 1A 1的tag-SNP rs7043217与PD易感性显著相关，其中T为危险等位基因（基因型频率，P = 0.030;等位基因频率，P = 0.013，OR = 1.258，95%CI = 1.050-1.508）。多个单倍型与PD风险异常相关，最高为4-SNP GGTA模块，顺序为rs 4646547、rs 1888202、rs7043217和rs647880（P = 9.610 × 10-8，OR = 6.420，95%CI = 2.944-13.998）。交互作用分析显示，同时存在rs7043217的CC基因型和ALDH 2变异体rs 4767944的TT基因型可增强PD的保护作用（P = 4.68 × 10-4，OR = 0.378，95%CI = 0.219-0.652）。PD组ALDH 1A 1 mRNA表达水平较对照组呈下降趋势（P = 0.084）。结论：我们的研究结果为ALDH 1在PD发病机制中的作用提供了新的遗传学见解。
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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影响因子：
44.1
作者：
Shi, YY;He, L
通讯作者：
He, L
影响因子：
15.1
作者：
Molochnikov L;Rabey JM;Dobronevsky E;Bonucelli U;Ceravolo R;Frosini D;Grünblatt E;Riederer P;Jacob C;Aharon-Peretz J;Bashenko Y;Youdim MB;Mandel SA
通讯作者：
Mandel SA
影响因子：
11
作者：
HUGHES, AJ;DANIEL, SE;LEES, AJ
通讯作者：
LEES, AJ
影响因子：
6.1
作者：
Galter, D;Buervenich, S;Olson, L
通讯作者：
Olson, L
影响因子：
168.9
作者：
Kalia, Lorraine V.;Lang, Anthony E.
通讯作者：
Lang, Anthony E.