title: A variant in the ABO gene explains the variation in soluble E-selectin levels-results from dense genotyping in two independent populations.
abstract: BACKGROUND
  Elevated soluble (s) E-selectin levels have been associated with various cardiovascular diseases. Recently, genetic variants in the ABO blood group have been related to E-selectin levels in a small cohort of patients with type 1 diabetes. We evaluated whether this association is reproducible in two large samples of Caucasians.
  
  
  RESULTS
  Data of the present study was drawn from the population-based MONICA/KORA Augsburg study (n = 1,482) and the patients-based LURIC study (n = 1,546). A high-density genotyping array (50K IBC Chip) containing single-nucleotide polymorphisms (SNPs) from E-selectin candidate genes selected on known biology of E-selectin metabolism, mouse genetic studies, and human genetic association studies, was used for genotyping. Linear regression analyses with adjustment for age and sex (and survey in KORA) were applied to assess associations between gene variants and sE-selectin concentrations. A number of 12 SNPs (in KORA) and 13 SNPs (in LURIC), all from the ABO blood group gene, were significantly associated with the log-transformed concentration of E-selectin. The strongest association was observed for rs651007 with a change of log-transformed sE-selectin per one copy of the minor allele of -0.37 ng/ml (p = 1.87×10(-103)) in KORA and -0.35 ng/ml (p = 5.11×10(-84)) in LURIC. Inclusion of rs651007 increased the explained sE-selectin variance by 0.256 in KORA and 0.213 in LURIC. All SNPs had minor allele frequencies above 20% showing a substantial gene variation.
  
  
  CONCLUSIONS
  Our findings in two independent samples indicate that the genetic variants at the ABO locus affect sE-selectin levels. Since distinct genome-wide association studies linked the ABO gene with myocardial infarction (MI) in the presence of coronary atherosclerosis and with coronary artery disease, these findings may not only enhance our understanding of adhesion molecule biology, but may also provide a focus for several novel research avenues.
authors.affiliation: Department of Internal Medicine II - Cardiology, University of Ulm Medical Centre, Ulm, Germany.
authors.forename: Mahir
authors.initials: M
authors.lastname: Karakas
authors.forename: Jens
authors.initials: J
authors.lastname: Baumert
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.forename: Barbara
authors.initials: B
authors.lastname: Thorand
authors.forename: Dhayana
authors.initials: D
authors.lastname: Dallmeier
authors.forename: Günther
authors.initials: G
authors.lastname: Silbernagel
authors.forename: Tanja B
authors.initials: TB
authors.lastname: Grammer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rottbauer
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology*; D004195:Disease Models, Animal; D019040:E-Selectin / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000017:ABO Blood-Group System; D019040:E-Selectin