Soluble P-selectin, SELP polymorphisms, and atherosclerotic risk in European-American and African-African young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
OBJECTIVE
To characterize the genetic and clinical correlates of soluble P-selectin, and the relationship of P-selectin to atherosclerotic risk, in young European-American (EA) and African-American (AA) adults.


RESULTS
We assessed the interrelationships between 25 common SELP polymorphisms, soluble P-selectin, and atherosclerotic risk in 1222 EA and 1072 AA from the longitudinal population-based CARDIA study. Male sex, smoking, blood pressure, and metabolic status were strong cross-sectional correlates of soluble P-selectin among CARDIA subjects aged 33 to 45 years, explaining 13% of the variance. Among EAs, higher soluble P-selectin predicted carotid intima-media thickness (IMT) measured 5 years later, even after accounting for traditional risk factors. Common SELP nucleotide sequence variants explained 11% and 5% of the interindividual variation in soluble P-selectin levels in EAs and AAs, respectively. Four distinct variants contributed to P-selectin phenotype in EAs, including a polymorphism of the 5' SELP haplotype block associated with carotid IMT. Half of the phenotypic variation attributable to SELP in EAs could be explained by the Thr715Pro polymorphism, whereas Val599Leu was more strongly associated with soluble P-selectin among AAs.


CONCLUSIONS
Common SELP polymorphisms were associated with soluble P-selectin and carotid IMT in young adults, but the patterns of association differed between EAs and AAs. These results support the role of P-selectin in the preclinical stages of atherosclerosis.
Departments of Epidemiology, University of Washington, Seattle, WA 98195, USA.
Alexander P
AP
Reiner
Christopher S
CS
Carlson
Bharat
B
Thyagarajan
Mark J
MJ
Rieder
Joseph F
JF
Polak
David S
DS
Siscovick
Deborah A
DA
Nickerson
David R
DR
Jacobs
Myron D
MD
Gross
D000328:Adult; D001741:Black or African American; D002340:Carotid Artery Diseases / Q000235:genetics* / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors; D017539:Tunica Intima / Q000473:pathology; D044465:White People
D019007:P-Selectin