Novel Association of ABO Histo-Blood Group Antigen with Soluble ICAM-1: Results of a Genome-Wide Association Study of 6,578 Women

While circulating levels of soluble Intercellular Adhesion Molecule 1 (sICAM-1) have been associated with diverse conditions including myocardial infarction, stroke, malaria, and diabetes, comprehensive analysis of the common genetic determinants of sICAM-1 is not available. In a genome-wide association study conducted among 6,578 participants in the Women's Genome Health Study, we find that three SNPs at the ICAM1 (19p13.2) locus (rs1799969, rs5498 and rs281437) are non-redundantly associated with plasma sICAM-1 concentrations at a genome-wide significance level (P<5×10−8), thus extending prior results from linkage and candidate gene studies. We also find that a single SNP (rs507666, P = 5.1×10−29) at the ABO (9q34.2) locus is highly correlated with sICAM-1 concentrations. The novel association at the ABO locus provides evidence for a previously unknown regulatory role of histo-blood group antigens in inflammatory adhesion processes.

尽管可溶性细胞间黏附分子1（soluble Intercellular Adhesion Molecule 1, sICAM-1）的循环水平已与心肌梗死、脑卒中、疟疾及糖尿病等多种病症相关，但目前尚无针对sICAM-1常见遗传决定因素的全面分析。本研究在一项针对女性基因组健康研究（Women's Genome Health Study）中6578名参与者开展的全基因组关联研究中发现，ICAM1基因座（19p13.2）处的3个单核苷酸多态性位点（rs1799969、rs5498及rs281437）与血浆sICAM-1浓度存在非冗余关联，且达到全基因组显著性水平（P<5×10⁻⁸），由此拓展了此前连锁研究与候选基因研究的成果。我们还发现，ABO基因座（9q34.2）处的单个单核苷酸多态性位点（rs507666, P=5.1×10⁻²⁹）与sICAM-1浓度高度相关。ABO基因座处的这一新关联，为组织血型抗原在炎症黏附过程中此前未被发现的调控作用提供了证据。