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Clinical and genetic correlates of soluble P-selectin in the community

D S Lee1, M G Larson, K L Lunetta

  • 1Institute for Clinical Evaluative Sciences and University Health Network, University of Toronto, Toronto, ON, Canada

Journal of Thrombosis and Haemostasis : JTH
|October 20, 2007
PubMed

Insights

Soluble P-selectin levels, linked to cardiovascular risk, are influenced by multiple clinical factors and a specific SELP gene variant. This genetic factor significantly explains variations in P-selectin concentrations beyond clinical correlates.

Area of Science:

  • Cardiovascular Disease Research
  • Genetics and Genomics
  • Biomarker Discovery

Background:

  • P-selectin is a cell adhesion molecule implicated in atherogenesis.
  • Soluble P-selectin concentrations serve as a biomarker for cardiovascular risk.
  • Clinical and genetic factors influencing soluble P-selectin require further elucidation.

Purpose of the Study:

  • To investigate the clinical correlates of circulating P-selectin.
  • To characterize the genetic associations of soluble P-selectin.
  • To examine P-selectin levels in diverse community populations.

Main Methods:

  • Analysis of cardiovascular risk factors and soluble P-selectin in Framingham Heart Study participants (Offspring and Omni cohorts).
  • Evaluation of P-selectin heritability, linkage, and association with 29 SELP single-nucleotide polymorphisms (SNPs) in pedigreed individuals.
  • Multivariable regression models to assess associations and explain variability.

Main Results:

  • Higher soluble P-selectin was associated with older age, male sex, minority status, smoking, obesity, hypertension, dyslipidemia, and diabetes.
  • Clinical factors accounted for 10.4% of interindividual P-selectin variability.
  • A SELP gene SNP (rs6136) significantly correlated with lower P-selectin levels, explaining 9.7% of variation independently of clinical factors.

Conclusions:

  • Circulating P-selectin concentrations are significantly associated with a range of clinical risk factors.
  • A specific single-nucleotide polymorphism in the SELP gene substantially influences P-selectin levels.
  • Genetic variation, particularly rs6136, plays a key role in determining soluble P-selectin concentrations.
Abstract

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