title: Soluble CD14: genomewide association analysis and relationship to cardiovascular risk and mortality in older adults.
abstract: OBJECTIVE
  CD14 is a glycosylphosphotidylinositol-anchored membrane glycoprotein expressed on neutrophils and monocytes/macrophages that also circulates as a soluble form (sCD14). Despite the well-recognized role of CD14 in inflammation, relatively little is known about the genetic determinants of sCD14 or the relationship of sCD14 to vascular- and aging-related phenotypes.
  
  
  RESULTS
  We measured baseline levels of sCD14 in >5000 European-American and black adults aged 65 years and older from the Cardiovascular Health Study, who were well characterized at baseline for atherosclerotic risk factors and subclinical cardiovascular disease, and who have been followed for clinical cardiovascular disease and mortality outcomes up to 20 years. At baseline, sCD14 generally showed strong positive correlations with traditional cardio-metabolic risk factors and with subclinical measures of vascular disease such as carotid wall thickness and ankle-brachial index (independently of traditional cardiovascular disease risk factors), and was also inversely correlated with body mass index. In genomewide association analyses of sCD14, we (1) confirmed the importance of the CD14 locus on chromosome 5q21 in European-American; (2) identified a novel African ancestry-specific allele of CD14 associated with lower sCD14 in blacks; and (3) identified a putative novel association in European-American of a nonsynonymous variant of PIGC, which encodes an enzyme required for the first step in glycosylphosphotidylinositol anchor biosynthesis. Finally, we show that, like other acute phase inflammatory biomarkers, sCD14 predicts incident cardiovascular disease, and strongly and independently predicts all-cause mortality in older adults.
  
  
  CONCLUSIONS
  CD14 independently predicts risk mortality in older adults.
authors.affiliation: Department of Epidemiology, Box 357236, University of Washington, Seattle, Washington 98195, USA. apreiner@u.washington.edu
authors.forename: Alex P
authors.initials: AP
authors.lastname: Reiner
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.forename: Paulo H M
authors.initials: PH
authors.lastname: Chaves
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Ellis
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Jeremy
authors.initials: J
authors.lastname: Walston
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
mesh_terms: D001741:Black or African American / Q000235:genetics; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000401:mortality*; D002895:Chromosomes, Human, Pair 5; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006602:Hexosyltransferases / Q000235:genetics; D006801:Humans; D015994:Incidence; D018836:Inflammation Mediators / Q000097:blood; D016014:Linear Models; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D015999:Multivariate Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D008565:Membrane Proteins; D006602:Hexosyltransferases; C101351:PIGC protein, human