P-selectin polymorphisms' influences on P-selectin serum concentrations and on their familial correlation: the STANISLAS family study.
BACKGROUND
P-selectin is an adhesion molecule known to be involved in the pathogenesis of several diseases through its major role in the initial phase of leukocytes recruitment during inflammation. However, genetic characterization of soluble P-selectin remains unclear.


OBJECTIVE
In the STANISLAS cohort, we study the familial correlations of P-selectin levels and investigate the association of six P-selectin polymorphisms (C-2123G, A-1969G, S290N, N562D, V599L and T715P) and cardiovascular risk factors with P-selectin concentrations.


METHODS
Full phenotypic and genotypic information was available for 136 healthy families composed of both natural parents and at least one child (boys, n = 125; and girls, n = 139) aged more than 4 years.


RESULTS
While no correlation was observed between spouses, family correlations of P-selectin concentrations were highly significant for sibling (0.50 +/- 0.12, P < 10(-3)) and child-parent pairs (0.42 +/- 0.04, P < 10(-3)). P-selectin haplotypes explained about 25% of the variability of P-selectin concentrations, this effect being mainly due to the additive effects of two polymorphisms, V599L and T715P. After adjusting for the effect of the P-selectin polymorphisms, the sibling and child-parent correlations decreased to (0.39 +/- 0.08, P < 10(-4)) and (0.32 +/- 0.06, P < 10(-4)), respectively.


CONCLUSIONS
In the present study, we showed that two P-selectin polymorphisms, V599L and T715P, explained about 25% of the variability of P-selectin concentrations and accounted for about 40% of their family resemblance. These results would suggest a genetic influence on P-selectin concentrations beyond the contribution of the P-selectin gene.
Marteau
J B
JB
INSERM, Equipe Génétique Cardiovasculaire du CIC 9501, Nancy, France.
Lambert
D
D
Herbeth
B
B
Marie
B
B
Droesch
S
S
Tregouet
D A
DA
Visvikis-Siest
S
S
D000328:Adult; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000235:genetics; D002448:Cell Adhesion; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012307:Risk Factors
D019007:P-Selectin