Genome-Wide Association Identifies the ABO Blood Group as a Major Locus Associated With Serum Levels of Soluble E-Selectin

被引:169
作者
Paterson, Andrew D. [1 ,4 ]
Lopes-Virella, Maria F. [5 ]
Waggott, Daryl [2 ]
Boright, Andrew P. [3 ]
Hosseini, S. Mohsen [1 ]
Carter, Rickey E. [6 ]
Shen, Enqing [2 ]
Mirea, Lucia [2 ,4 ]
Bharaj, Bhupinder [1 ]
Sun, Lei [4 ]
Bull, Shelley B. [2 ,4 ]
机构
[1] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1L7, Canada
[2] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada
[3] Univ Toronto, Dept Med, Univ Hlth Network, Toronto, ON M5S 1A1, Canada
[4] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada
[5] Med Univ S Carolina, Dept Med & Lab Serv, Charleston, SC USA
[6] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC USA
基金
加拿大健康研究院; 美国国家卫生研究院;
关键词
E-selectin; ABO blood group; genome-wide association; SNP; CELLULAR ADHESION MOLECULES; LEUKOCYTE-ENDOTHELIAL ADHESION; PLASMODIUM-FALCIPARUM MALARIA; RISK-FACTORS; CARDIOVASCULAR-DISEASE; VASCULAR-DISEASE; MARKERS; DYSFUNCTION; DETERMINANTS; NEPHROPATHY;
D O I
10.1161/ATVBAHA.109.192971
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-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. Methods and Results-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. Conclusion-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. (Arterioscler Thromb Vasc Biol. 2009; 29: 1958-1967.)
引用
收藏
页码:1958 / U609
页数:26
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