遗传易感性改变了长期空气污染暴露与帕金森病之间的关联。

Genetic susceptibility modifies the association of long-term air pollution exposure on Parkinson's disease.

作者信息

Huang Yi-Ming, Ma Ya-Hui, Gao Pei-Yang, Cui Xi-Han, Hou Jia-Hui, Chi Hao-Chen, Fu Yan, Wang Zhi-Bo, Feng Jian-Feng, Cheng Wei, Tan Lan, Yu Jin-Tai

机构信息

Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.

出版信息

NPJ Parkinsons Dis. 2024 Jan 17;10(1):23. doi: 10.1038/s41531-024-00633-1.

Abstract

Inconsistent findings exist regarding the potential association between polluted air and Parkinson's disease (PD), with unclear insights into the role of inherited sensitivity. This study sought to explore the potential link between various air pollutants and PD risk, investigating whether genetic susceptibility modulates these associations. The population-based study involved 312,009 initially PD-free participants with complete genotyping data. Annual mean concentrations of PM, PM, NO, and NO were estimated, and a polygenic risk score (PRS) was computed to assess individual genetic risks for PD. Cox proportional risk models were employed to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between ambient air pollutants, genetic risk, and incident PD. Over a median 12.07-year follow-up, 2356 PD cases (0.76%) were observed. Compared to the lowest quartile of air pollution, the highest quartiles of NO and PM pollution showed HRs and 95% CIs of 1.247 (1.089-1.427) and 1.201 (1.052-1.373) for PD incidence, respectively. Each 10 μg/m increase in NO and PM yielded elevated HRs and 95% CIs for PD of 1.089 (1.026-1.155) and 1.363 (1.043-1.782), respectively. Individuals with significant genetic and PM exposure risks had the highest PD development risk (HR: 2.748, 95% CI: 2.145-3.520). Similarly, those with substantial genetic and NO exposure risks were over twice as likely to develop PD compared to minimal-risk counterparts (HR: 2.414, 95% CI: 1.912-3.048). Findings suggest that exposure to air contaminants heightens PD risk, particularly in individuals genetically predisposed to high susceptibility.

摘要

关于空气污染与帕金森病(PD)之间的潜在关联,研究结果并不一致,对于遗传易感性所起的作用也缺乏清晰的认识。本研究旨在探讨各种空气污染物与PD风险之间的潜在联系,研究遗传易感性是否会调节这些关联。这项基于人群的研究纳入了312,009名最初无PD且具有完整基因分型数据的参与者。估算了PM、PM、NO和NO的年平均浓度,并计算了多基因风险评分(PRS)以评估个体患PD的遗传风险。采用Cox比例风险模型计算环境空气污染物、遗传风险与新发PD之间关联的风险比(HR)和95%置信区间(CI)。在中位12.07年的随访期内,观察到2356例PD病例(0.76%)。与空气污染最低四分位数相比,NO和PM污染最高四分位数的PD发病率的HR和95%CI分别为1.247(1.089 - 1.427)和1.201(1.052 - 1.373)。NO和PM每增加10μg/m,PD的HR和95%CI分别升高至1.089(1.026 - 1.155)和1.363(1.043 - 1.782)。具有显著遗传和PM暴露风险的个体患PD的风险最高(HR:2.748,95%CI:2.145 - 3.520)。同样,与低风险个体相比,具有显著遗传和NO暴露风险的个体患PD的可能性高出两倍多(HR:2.414,95%CI:1.912 - 3.048)。研究结果表明,接触空气污染物会增加PD风险,尤其是在具有遗传易感性的个体中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/078a/10794179/212772885025/41531_2024_633_Fig1_HTML.jpg

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