title: Integrative omics approach identifies interleukin-16 as a biomarker of emphysema.
abstract: Interleukin-16 (IL-16) is a multifunctional cytokine that has been associated with autoimmune and allergic diseases. To investigate comprehensively whether IL-16 is also associated with chronic obstructive pulmonary disease (COPD) and emphysema, we performed an integrated analysis of multiple "omics" data. Over 500 subjects participating in the COPDGene® study donated blood and were clinically characterized and genetically profiled. IL-16 mRNA levels were measured in peripheral blood mononuclear cells (PBMC), and protein levels were measured in fresh frozen plasma. A multivariate analysis found plasma IL-16 positively associated with age and body mass index, and negatively associated with current smoking and emphysema in the upper lobes. PBMC IL-16 expression was positively associated with gender and a composite score for airflow obstruction, emphysema, and gas trapping. Whole-genome expression quantitative trait locus (eQTL) analysis identified a novel IL-16 missense SNP (rs11556218) associated with lower IL-16 in plasma. In summary, an integrated "omics" analysis in a very large cohort identified an association between decreased IL-16 and emphysema and discovered a novel IL-16 cis-eQTL. Thus IL-16 plasma levels and IL-16 genotyping may be useful in a personalized medicine approach for lung disease.
authors.affiliation: 1 Department of Medicine, National Jewish Health , Denver, Colorado.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Bahr
authors.forename: Grant
authors.initials: G
authors.lastname: Hughes
authors.forename: Sharon
authors.initials: S
authors.lastname: Lutz
authors.forename: Yu-Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Coldren
authors.forename: Nichole
authors.initials: N
authors.lastname: Reisdorph
authors.forename: Katerina J
authors.initials: KJ
authors.lastname: Kechris
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004646:Emphysema / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D019410:Interleukin-16 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040901:Proteomics; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D040641:Quantitative Trait Loci; D012907:Smoking / Q000009:adverse effects / Q000097:blood
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D019410:Interleukin-16