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Clinical correlates, heritability, and genetic linkage of circulating CD40 ligand in the Framingham Offspring Study

John F Keaney1, Izabella Lipinska, Martin G Larson

  • 1Evans Memorial Department of Medicine, Boston University School of Medicine, Boston, MA, USA. john.keaney@umassmed.edu

American Heart Journal
|December 9, 2008
PubMed

Insights

Soluble CD40 ligand (sCD40L) levels in blood are poorly linked to traditional cardiovascular disease risk factors. Genetic factors play a modest role, but more research is needed to understand sCD40L

Area of Science:

  • Cardiovascular Science
  • Immunology
  • Genetics

Background:

  • The CD40 receptor and its ligand (CD40L) influence inflammation and thrombosis, key factors in atherosclerosis.
  • Elevated soluble CD40L (sCD40L) levels are associated with cardiovascular risk in specific patient groups.

Purpose of the Study:

  • To identify predictors of sCD40L concentration in a large, community-based population.
  • To investigate the relationship between sCD40L and established cardiovascular disease (CVD) risk factors.

Main Methods:

  • Serum and plasma sCD40L concentrations were measured in 3,259 participants from the Framingham Offspring Study.
  • Multivariable regression models were used to analyze predictors of sCD40L.

Main Results:

  • Advancing age was the sole consistent inverse correlate of both serum and plasma sCD40L.
  • Clinical covariates explained minimal variability in sCD40L (1.4% serum, 2.7% plasma).
  • Genetic factors accounted for a modest portion of the adjusted variability in sCD40L (12% serum, 14% plasma).

Conclusions:

  • Circulating sCD40L shows weak association with common CVD risk factors.
  • sCD40L exhibits moderate heritability.
  • Longitudinal studies are necessary to determine the predictive value of serum and plasma sCD40L for CVD risk in the general population.
Abstract

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