Association of Variation at the ABO Locus With Circulating Levels of Soluble Intercellular Adhesion Molecule-1, Soluble P-selectin, and Soluble E-selectin

Author:

Kiechl Stefan1,Paré Guillaume1,Barbalic Maja1,Qi Lu1,Dupuis Josée1,Dehghan Abbas1,Bis Joshua C.1,Laxton Ross C.1,Xiao Qingzhong1,Bonora Enzo1,Willeit Johann1,Xu Qingbo1,Witteman Jacqueline C.M.1,Chasman Daniel1,Tracy Russell P.1,Ballantyne Christie M.1,Ridker Paul M.1,Benjamin Emelia J.1,Ye Shu1

Affiliation:

1. From Innsbruck Medical University (S.K., J.W.), Innsbruck, Austria; McMaster University (G.P.), Hamilton, Ontario, Canada; the University of Texas Health Science Center at Houston (M.B.), Houston, TX; Harvard Med School (L.Q.), Boston, MA; the National Heart, Lung, and Blood Institute & Framingham Heart Study (J.D., E.J.B.), Boston, MA; Boston University School of Public Health (J.D., E.J.B.), Boston, MA; Erasmus Med Center (A.D., J.C.M.W.), Rotterdam, The Netherlands; the Netherlands Consortium...

Abstract

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. Methods and 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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Genetics(clinical),Cardiology and Cardiovascular Medicine,Genetics

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