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

D. S. Lee, M. G. Larson, K. L. Lunetta, J. Dupuis, J. Rong, J. F. Keaney, I. Lipinska, C. T. Baldwin, R. S. Vasan, Emelia J. Benjamin

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Background: P-selectin is a cell adhesion molecule that is involved in atherogenesis, and soluble concentrations of this biomarker reflect cardiovascular risk. However, the clinical correlates and genetic characterization of soluble P-selectin have not been clearly elucidated. Objective: To describe clinical and genetic correlates of circulating P-selectin in the community. Methods: In Framingham Heart Study Offspring (European descent) and Omni (ethnic/racial minority) participants, we examined the association of cardiovascular risk factors with soluble P-selectin concentrations. In Offspring participants, we evaluated heritability, linkage and association of 29 SELP single-nucleotide polymorphisms (SNPs) with adjusted P-selectin concentrations. Rasults: In multivariable analysis of 3690 participants (54% women, mean age 60±10years), higher log-transformed P-selectin concentrations were inversely associated with female sex and hormone replacement therapy, and positively associated with age, ethnic/racial minority status, cigarette smoking, waist circumference, systolic blood pressure, fasting glucose, and total/high-density lipoprotein cholesterol and triglyceride concentrations. Clinical factors explained 10.4% of the interindividual variability in P-selectin concentrations. In 571 extended pedigrees (n = 1841) with ≥2 phenotyped members per family, multivariable-adjusted heritability was 45.4±5.8%. Among the SELP SNPs examined, a non-synonymous SNP (rs6136) encoding a threonine-to-proline substitution at position 715 was highly significantly associated with decreased P-selectin concentrations (P = 5.2×10-39), explaining 9.7% of variation after adjustment for clinical factors. Conclusion: Multiple clinical factors and an SNP in the SELP gene were significantly associated with circulating P-selectin concentrations. One SNP in SELP explained significant variation in circulating P-selectin concentrations, even after accounting for known clinical correlates.

Original languageEnglish (US)
Pages (from-to)20-31
Number of pages12
JournalJournal of Thrombosis and Haemostasis
Volume6
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

Keywords

  • Epidemiology
  • Genetics
  • Inflammation
  • P-selectin
  • Polymorphism single nucleotide
  • Risk factors

ASJC Scopus subject areas

  • Hematology

Fingerprint

Dive into the research topics of 'Clinical and genetic correlates of soluble P-selectin in the community'. Together they form a unique fingerprint.

Cite this