Association of variation at the ABO locus with circulating levels of soluble intercellular adhesion molecule-1, soluble P-selectin, and soluble E-selectin: a meta-analysis.
BACKGROUND
Circulating levels of soluble intercellular adhesion molecule-1, soluble P-selectin, and soluble E-selectin have been associated with variation at the ABO locus. To evaluate these associations and the effect sizes, we performed a meta-analysis with new and previous reported data for polymorphism rs579459.


RESULTS
Compared with major allele homozygotes, heterozygotes and minor allele homozygotes had 4.6% (95% CI, 3.4%-5.8%, P=7.3 × 10(-14)) and 7.2% (95% CI, 4.7%-9.7%, P=1.5 × 10(-8)), respectively, lower soluble intercellular adhesion molecule-1 levels (n=33 671). An allele dose-dependent association also was observed for soluble P-selectin (n=4921) with heterozygotes and minor allele homozygotes having 11.5% (95% CI, 7.2%-15.8%, P=1.7 × 10(-7)) and 18.6% (95% CI, 9.1%-28.1%, P=1.2 × 10(-4)), respectively, lower levels than in major allele homozygotes. A larger effect size, again consistent with an additive genetic model, was seen for soluble E-selectin (n=2860) whose level was 25.6% (95% CI, 19.0%-32.2%, P=2.1 × 10(-14)) lower in heterozygotes and 43.3% (95% CI, 36.9%-49.3%, P=4.3 × 10(-42)) lower in minor allele homozygotes than in major allele homozygotes.


CONCLUSIONS
The data support the association of variation at the ABO locus with soluble intercellular adhesion molecule-1, soluble P-selectin, and soluble E-selectin levels.
Innsbruck Medical University, Innsbruck, Austria.
Stefan
S
Kiechl
Guillaume
G
Paré
Maja
M
Barbalic
Lu
L
Qi
Josée
J
Dupuis
Abbas
A
Dehghan
Joshua C
JC
Bis
Ross C
RC
Laxton
Qingzhong
Q
Xiao
Enzo
E
Bonora
Johann
J
Willeit
Qingbo
Q
Xu
Jacqueline C M
JC
Witteman
Daniel
D
Chasman
Russell P
RP
Tracy
Christie M
CM
Ballantyne
Paul M
PM
Ridker
Emelia J
EJ
Benjamin
Shu
S
Ye
D000017:ABO Blood-Group System / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D019040:E-Selectin / Q000097:blood*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood*; D020641:Polymorphism, Single Nucleotide
D000017:ABO Blood-Group System; D019040:E-Selectin; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1