Kiechl Stefan, Paré Guillaume, Barbalic Maja, Qi Lu, Dupuis Josée, Dehghan Abbas, Bis Joshua C, Laxton Ross C, Xiao Qingzhong, Bonora Enzo, Willeit Johann, Xu Qingbo, Witteman Jacqueline C M, Chasman Daniel, Tracy Russell P, Ballantyne Christie M, Ridker Paul M, Benjamin Emelia J, Ye Shu
Innsbruck Medical University, Innsbruck, Austria.
Circ Cardiovasc Genet. 2011 Dec;4(6):681-6. doi: 10.1161/CIRCGENETICS.111.960682. Epub 2011 Oct 18.
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.
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.
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.
可溶性细胞间黏附分子-1、可溶性P-选择素和可溶性E-选择素的循环水平与ABO基因座的变异有关。为了评估这些关联及效应大小，我们对多态性rs579459的新数据和先前报道的数据进行了荟萃分析。
与主要等位基因纯合子相比，杂合子和次要等位基因纯合子的可溶性细胞间黏附分子-1水平分别降低了4.6%（95%CI，3.4%-5.8%，P=7.3×10⁻¹⁴）和7.2%（95%CI，4.7%-9.7%，P=1.5×10⁻⁸）（n=33671）。对于可溶性P-选择素（n=4921）也观察到了等位基因剂量依赖性关联，杂合子和次要等位基因纯合子的水平分别比主要等位基因纯合子低11.5%（95%CI，7.2%-15.8%，P=1.7×10⁻⁷）和18.6%（95%CI，9.1%-28.1%，P=1.2×10⁻⁴）。对于可溶性E-选择素（n=2860），观察到更大的效应大小，同样符合加性遗传模型，杂合子的水平比主要等位基因纯合子低25.6%（95%CI，19.0%-32.2%，P=2.1×10⁻¹⁴），次要等位基因纯合子的水平比主要等位基因纯合子低43.3%（95%CI，36.9%-49.3%，P=4.3×10⁻⁴²）。
数据支持ABO基因座变异与可溶性细胞间黏附分子-1、可溶性P-选择素和可溶性E-选择素水平之间的关联。
