Metabolomic Profiling Reveals Sex Specific Associations with Chronic Obstructive Pulmonary Disease and Emphysema

Metabolites

卷:11

JerryA. Krishnan¹  VictorE. Ortega²  DawnL. DeMeo³  LucasA. Gillenwater⁴  Wanda O’Neal⁵  KaterinaJ. Kechris⁶  KatherineA. Pratte⁷  Irina Petrache⁷  RussellP. Bowler⁷  WassimW. Labaki⁸  Nichole Reisdorph⁹ 

[1] Breathe Chicago Center, University of Illinois at Chicago, Chicago, IL 60608, USA;

[2] Center for Precision Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA;

[3] Channing Division of Network Medicine, and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;

[4] Computational Bioscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;

[5] Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;

[6] Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;

[7] Division of Medicine, National Jewish Health, Denver, CO 80206, USA;

[8] Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI 48109, USA;

[9] Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;

关键词: COPD;    emphysema;    sex differences;    network analysis;    WGCNA;    lung;   

DOI  :  10.3390/metabo11030161

来源: DOAJ

【 摘 要 】

Susceptibility and progression of lung disease, as well as response to treatment, often differ by sex, yet the metabolic mechanisms driving these sex-specific differences are still poorly understood. Women with chronic obstructive pulmonary disease (COPD) have less emphysema and more small airway disease on average than men, though these differences become less pronounced with more severe airflow limitation. While small studies of targeted metabolites have identified compounds differing by sex and COPD status, the sex-specific effect of COPD on systemic metabolism has yet to be interrogated. Significant sex differences were observed in 9 of the 11 modules identified in COPDGene. Sex-specific associations by COPD status and emphysema were observed in 3 modules for each phenotype. Sex stratified individual metabolite associations with COPD demonstrated male-specific associations in sphingomyelins and female-specific associations in acyl carnitines and phosphatidylethanolamines. There was high preservation of module assignments in SPIROMICS (SubPopulations and InteRmediate Outcome Measures In COPD Study) and similar female-specific shift in acyl carnitines. Several COPD associated metabolites differed by sex. Acyl carnitines and sphingomyelins demonstrate sex-specific abundances and may represent important metabolic signatures of sex differences in COPD. Accurately characterizing the sex-specific molecular differences in COPD is vital for personalized diagnostics and therapeutics.

【 授权许可】

Unknown