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Meta-Analysis
. 2011 Dec;4(6):681-6.
doi: 10.1161/CIRCGENETICS.111.960682. Epub 2011 Oct 18.

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

Stefan Kiechl  1 , Guillaume Paré, Maja Barbalic, Lu Qi, Josée Dupuis, Abbas Dehghan, Joshua C Bis, Ross C Laxton, Qingzhong Xiao, Enzo Bonora, Johann Willeit, Qingbo Xu, Jacqueline C M Witteman, Daniel Chasman, Russell P Tracy, Christie M Ballantyne, Paul M Ridker, Emelia J Benjamin, Shu Ye
Affiliations
Meta-Analysis

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

Stefan Kiechl et al. Circ Cardiovasc Genet. 2011 Dec.

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.

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Conflict of interest statement

Conflict of Interest Disclosures:

Stefan Kiechl received research grants; TRP188-B12 FWF. Lu Qi received research grants from NIH. Russell P. Tracyreceived other research support from Celera. Paul M Ridker received research grants from AstraZeneca, Novartis, Merck, NHLBI, and NCI. He received other support from Amgen and Celera as well as honorarium from several universities. He has ownership/interest in a patents relate to inflammatory biomarkers. Also, he is a consultant or serves on the advisory board for ISIS, Merck, Vascular Biogenics, and Abbott. Emelia J. Benjamin received research grants; R01HL09257, RC1HL101056, RO1HL102214, RO1AG028321. She also consults or is on advisory committees for NIH and NHLBI.

Figures

Figure 1
Figure 1
Weighted mean difference by genotype in soluble intercellular adhesion molecule-1 (sICAM-1), soluble P-selectin (sP-selectin), and soluble E-selectin (sE-selectin) levels. Data shown are weighted mean difference ± 95% confidence interval in circulating levels of sICAM-1 (panel A), sP-selectin (panel B) and sE-selectin (panel C), comparing heterozygotes or minor allele homozygotes, to major allele homozygotes, in a random-effects model.
Figure 1
Figure 1
Weighted mean difference by genotype in soluble intercellular adhesion molecule-1 (sICAM-1), soluble P-selectin (sP-selectin), and soluble E-selectin (sE-selectin) levels. Data shown are weighted mean difference ± 95% confidence interval in circulating levels of sICAM-1 (panel A), sP-selectin (panel B) and sE-selectin (panel C), comparing heterozygotes or minor allele homozygotes, to major allele homozygotes, in a random-effects model.
Figure 1
Figure 1
Weighted mean difference by genotype in soluble intercellular adhesion molecule-1 (sICAM-1), soluble P-selectin (sP-selectin), and soluble E-selectin (sE-selectin) levels. Data shown are weighted mean difference ± 95% confidence interval in circulating levels of sICAM-1 (panel A), sP-selectin (panel B) and sE-selectin (panel C), comparing heterozygotes or minor allele homozygotes, to major allele homozygotes, in a random-effects model.
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