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

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%, P7.31014) and 7.2 % (95 % CI, 4.7%–9.7%, P1.5108), respectively, lower soluble intercellular adhesion molecule-1 levels (n33 671). An allele dose-dependent association also was observed for soluble P-selectin (n4921) with heterozygotes and minor allele homozygotes having 11.5 % (95% CI, 7.2%–15.8%, P1.7107) and 18.6 % (95 % CI, 9.1%–28.1%, P1.2104), 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 (n2860) whose level was 25.6 % (95 % CI, 19.0%–32.2%, P2.11014) lower in heterozygotes and 43.3 % (95 % CI, 36.9% – 49.3%, P4.31042) 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. (Circ Cardiovasc Genet. 2011;4:681-686.) Key Words: cell adhesion molecules cardiovascular disease genetics plasm