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法国EGEA研究中荧光氧化产物与成年人吸烟状况的全基因组关联研究。

Genome-Wide Association Study of Fluorescent Oxidation Products Accounting for Tobacco Smoking Status in Adults from the French EGEA Study.

作者信息

Orsi Laurent, Margaritte-Jeannin Patricia, Andrianjafimasy Miora, Dumas Orianne, Mohamdi Hamida, Bouzigon Emmanuelle, Demenais Florence, Matran Régis, Zerimech Farid, Nadif Rachel, Dizier Marie-Hélène

机构信息

Université Paris-Saclay, UVSQ, Univ. Paris-Sud, INSERM, Équipe d'Epidémiologie Respiratoire Intégrative, CESP, 94807 Villejuif, France.

Université Paris Cité, INSERM, UMR 1124, Group of Genomic Epidemiology and Multifactorial Diseases, 75006 Paris, France.

出版信息

Antioxidants (Basel). 2022 Apr 20;11(5):802. doi: 10.3390/antiox11050802.

Abstract

Oxidative stress (OS) is the main pathophysiological mechanism involved in several chronic diseases, including asthma. Fluorescent oxidation products (FlOPs), a global biomarker of damage due to OS, is of growing interest in epidemiological studies. We conducted a genome-wide association study (GWAS) of the FlOPs level in 1216 adults from the case-control and family-based EGEA study (mean age 43 years old, 51% women, and 23% current smokers) to identify genetic variants associated with FlOPs. The GWAS was first conducted in the whole sample and then stratified according to smoking status, the main exogenous source of reactive oxygen species. Among the top genetic variants identified by the three GWAS, those located in ( = 3 × 10), near ( = 9 × 10), in ( = 4 × 10), and near ( = 2 × 10) are the most relevant because of both their link to biological pathways related to OS and their association with several chronic diseases for which the role of OS in their pathophysiology has been pointed out. and are of particular interest due to their involvement in the same biological pathways related to OS and their functional interaction. To conclude, this study, which is the first GWAS of FlOPs, provides new insights into the pathophysiology of chronic OS-related diseases.

摘要

氧化应激(OS)是包括哮喘在内的多种慢性疾病所涉及的主要病理生理机制。荧光氧化产物(FlOPs)作为OS所致损伤的一种整体生物标志物,在流行病学研究中越来越受到关注。我们对来自病例对照和基于家系的EGEA研究的1216名成年人(平均年龄43岁,51%为女性,23%为当前吸烟者)的FlOPs水平进行了全基因组关联研究(GWAS),以确定与FlOPs相关的基因变异。GWAS首先在整个样本中进行,然后根据吸烟状况(活性氧的主要外源性来源)进行分层。在三项GWAS确定的顶级基因变异中,位于(=3×10)、靠近(=9×10)、位于(=4×10)以及靠近(=2×10)的变异最为相关,这是因为它们既与OS相关的生物途径有关,又与几种已指出OS在其病理生理学中起作用的慢性疾病相关。由于和参与了与OS相关的相同生物途径以及它们的功能相互作用,因此它们特别令人感兴趣。总之,这项作为首次对FlOPs进行的GWAS研究,为慢性OS相关疾病的病理生理学提供了新的见解。

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