TY - JOUR
T1 - Clinical and genetic correlates of soluble P-selectin in the community
AU - Lee, D. S.
AU - Larson, M. G.
AU - Lunetta, K. L.
AU - Dupuis, J.
AU - Rong, J.
AU - Keaney, J. F.
AU - Lipinska, I.
AU - Baldwin, C. T.
AU - Vasan, R. S.
AU - Benjamin, Emelia J.
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
KW - Epidemiology
KW - Genetics
KW - Inflammation
KW - P-selectin
KW - Polymorphism single nucleotide
KW - Risk factors
UR - https://www.scopus.com/pages/publications/37548998609
UR - https://www.scopus.com/pages/publications/37548998609#tab=citedBy
U2 - 10.1111/j.1538-7836.2007.02805.x
DO - 10.1111/j.1538-7836.2007.02805.x
M3 - Article
C2 - 17944986
AN - SCOPUS:37548998609
SN - 1538-7933
VL - 6
SP - 20
EP - 31
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 1
ER -