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


RESULTS
In multivariable analysis of 3,690 participants (54% women, mean age 60 +/- 10 years), 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 = 1,841) with >or= 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 x 10(-39)), explaining 9.7% of variation after adjustment for clinical factors.


CONCLUSIONS
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.
Lee
D S
DS
Institute for Clinical Evaluative Sciences and University Health Network, University of Toronto, Toronto, ON, Canada
Larson
M G
MG
Lunetta
K L
KL
Dupuis
J
J
Rong
J
J
Keaney
J F
JF
Lipinska
I
I
Baldwin
C T
CT
Vasan
R S
RS
Benjamin
E J
EJ
D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019007:P-Selectin / Q000097:blood*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012111:Residence Characteristics; D012307:Risk Factors
D019007:P-Selectin