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

Abstract

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.

Genetic Regulation of Serum Phytosterol Levels and Risk of Coronary Artery Disease

“…However, it is of great interest that ABO has been associated recently in a number of hypothesis-free genome-wide associations with a diverse set of phenotypes, such as pancreatic cancer or plasma levels of intercellular adhesion molecule-1. 36,37 These data suggest that ABO effects on these phenotypes may indeed underlie a common mechanism that still needs to be determined.…”

ABO and Rh Blood Groups in Relation to Ovarian, Endometrial and Cervical Cancer Risk Among The Population of South-East Siberia

“…Therefore, carriers of blood group A may have diminished tumor immune response due to reduced ability to recognize and attack tumor cells that express Forssmann antigen. Finally, it should be noted that several studies have demonstrated an association between ABO genotype and altered levels of soluble E-selectin, ICAM-1, and tumor necrosis factor-alpha (Pare et al, 2008;Paterson et al, 2009a, Paterson et al, 2009b which also may suggest potential role of ABO in cancer development.…”

ABO blood group, hepatitis B viral infection and risk of pancreatic cancer

“…Several studies have demonstrated that ABO blood group antigen may alter the systemic inflammatory response. Genome-wide association studies have found an association between genetic variation in the first intron of the ABO genes and circulation levels of serum tumor necrosis factor alpha, 47 soluble intracellular adhesion molecule 48 and plasma levels of alkaline phosphatase. 49 Acute pancreatitis may be a complication of acute hepatitis infection.…”