Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD
| Autor: | Naz, Shama, Kolmert, Johan, Yang, Mingxing, Reinke, Stacey N, Kamleh, Muhammad Anas, Snowden, Stuart, Heyder, Tina, Levänen, Bettina, Erle, David J, Sköld, C Magnus, Wheelock, Åsa M, Wheelock, Craig E |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Chronic Obstructive Chronic Obstructive Pulmonary Disease Statistics as Topic Respiratory System Medical and Health Sciences Pulmonary Disease Sex Factors Tobacco Humans Metabolomics 2.1 Biological and endogenous factors Aetiology Lung Sweden Chromatography Liquid Tobacco Smoke and Health Phosphoric Diester Hydrolases Smoking Middle Aged respiratory tract diseases Respiratory Function Tests MicroRNAs Oxidative Stress Cross-Sectional Studies Good Health and Well Being Respiratory Female |
| Zdroj: | The European respiratory journal, vol 49, iss 6 |
| Popis: | Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I-II/A-B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography-high resolution mass spectrometry metabolomics platform.Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10-7). Sex stratification indicated that the separation was driven by females (p=2.4×10-7) relative to males (p=4.0×10-4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10-3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p |
| Databáze: | OpenAIRE |
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