Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin.
Arterioscler Thromb Vasc Biol
; 29(11): 1958-67, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-19729612
ABSTRACT
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 ANDRESULTS:
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.CONCLUSIONS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistema ABO de Grupos Sanguíneos
/
Selectina E
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Predisposição Genética para Doença
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Diabetes Mellitus Tipo 1
/
Estudo de Associação Genômica Ampla
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article