Hospital for Sick Children, Toronto, Ontario, Canada.
Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1958-67. doi: 10.1161/ATVBAHA.109.192971. Epub 2009 Sep 3.
Elevated serum soluble E-selectin levels have been associated with a number of diseases. Although E-selectin levels are heritable, little is known about the specific genetic factors involved. E-selectin levels have been associated with the ABO blood group phenotype.
We performed a high-resolution genome-wide association study of serum soluble E-selectin levels in 685 white individuals with type 1 diabetes from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study to identify major loci influencing levels. Highly significant evidence for association (P=10(-29)) was observed for rs579459 near the ABO blood group gene, accounting for 19% of the variance in E-selectin levels. Levels of E-selectin were higher in O/O than O/A heterozygotes, which were likewise higher than A/A genotypes. Analysis of subgroups of A alleles reveals heterogeneity in the association, and even after this was accounted for, an intron 1 SNP remained significantly associated. We replicate the ABO association in nondiabetic individuals.
ABO is a major locus for serum soluble E-selectin levels. We excluded population stratification, fine-mapped the association to sub-A alleles, and also document association with additional variation in the ABO region.
血清可溶性 E-选择素水平升高与许多疾病有关。尽管 E-选择素水平是可遗传的，但涉及的具体遗传因素知之甚少。E-选择素水平与 ABO 血型表型有关。
我们对来自糖尿病控制和并发症试验（DCCT）/糖尿病干预和并发症的流行病学（EDIC）研究的 685 名 1 型糖尿病白种个体的血清可溶性 E-选择素水平进行了高分辨率全基因组关联研究，以确定影响水平的主要基因座。在 ABO 血型基因附近的 rs579459 处观察到与 E-选择素水平显著相关（P=10(-29)），占 E-选择素水平变异的 19%。O/O 个体的 E-选择素水平高于 O/A 杂合子，而 O/A 杂合子又高于 A/A 基因型。对 A 等位基因亚组的分析显示，该关联存在异质性，即使考虑到这一点，内含子 1 SNP 仍然与该关联显著相关。我们在非糖尿病个体中复制了 ABO 关联。
ABO 是血清可溶性 E-选择素水平的主要基因座。我们排除了群体分层，将关联精细映射到亚 A 等位基因，并记录了 ABO 区域中额外变异的关联。
