title: Clinical correlates, heritability, and genetic linkage of circulating CD40 ligand in the Framingham Offspring Study.
abstract: BACKGROUND
  The CD40 receptor and its ligand (CD40L) are known to modulate both inflammation and thrombosis-2 processes important for the development and clinical expression of atherosclerosis. Circulating soluble CD40L (sCD40L) concentration predicts cardiovascular risk in selected patient samples. The purpose of this study was to determine the predictors of sCD40L in a large, community-based sample.
  
  
  METHODS
  We determined both serum and plasma sCD40L concentration in 3,259 participants (54% women) from the Framingham Offspring Study.
  
  
  RESULTS
  In multivariable models, advancing age was the only consistent (inverse) correlate of both serum and plasma sCD40L concentration. Overall, the variability explained by clinical covariates was very low for both measurements of sCD40L; with values of only 1.4% and 2.7% for serum and plasma, respectively. We observed that genetic factors accounted for a modest (12% serum; 14% plasma) amount of the adjusted variability in sCD40L.
  
  
  CONCLUSIONS
  Circulating sCD40L concentration was poorly associated with known cardiovascular disease (CVD) risk factors and was modestly heritable. Determining if either serum or plasma sCD40L are predictive of CVD risk in the community will require longitudinal follow-up.
authors.affiliation: Evans Memorial Department of Medicine, Boston University School of Medicine, Boston, MA, USA. john.keaney@umassmed.edu
authors.forename: John F
authors.initials: JF
authors.lastname: Keaney
authors.forename: Izabella
authors.initials: I
authors.lastname: Lipinska
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Josée
authors.initials: J
authors.lastname: Dupuis
authors.forename: Jane E
authors.initials: JE
authors.lastname: Freedman
authors.forename: Naomi M
authors.initials: NM
authors.lastname: Hamburg
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.forename: Jian
authors.initials: J
authors.lastname: Rong
authors.forename: Patrice
authors.initials: P
authors.lastname: Sutherland
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Vita
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
mesh_terms: D023201:CD40 Ligand / Q000097:blood* / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D023201:CD40 Ligand