title: Genome-Wide Association Study Identifies That the ABO Blood Group System Influences Interleukin-10 Levels and the Risk of Clinical Events in Patients with Acute Coronary Syndrome.
abstract: BACKGROUND
  Acute coronary syndrome (ACS) is a major cause of mortality worldwide. We have previously shown that increased interleukin-10 (IL-10) levels are associated with poor outcome in ACS patients.
  
  
  METHODS
  We performed a genome-wide association study in 2864 ACS patients and 408 healthy controls, to identify genetic variants associated with IL-10 levels. Then haplotype analyses of the identified loci were done and comparisons to levels of IL-10 and other known ACS related biomarkers.
  
  
  RESULTS
  Genetic variants at the ABO blood group locus associated with IL-10 levels (top SNP: rs676457, P = 4.4 × 10-10) were identified in the ACS patients. Haplotype analysis, using SNPs tagging the four main ABO antigens (A1, A2, B and O), showed that O and A2 homozygous individuals, or O/A2 heterozygotes have much higher levels of IL-10 compared to individuals with other antigen combinations. In the ACS patients, associations between ABO antigens and von Willebrand factor (VWF, P = 9.2 × 10-13), and soluble tissue factor (sTF, P = 8.6 × 10-4) were also found. In the healthy control cohort, the associations with VWF and sTF were similar to those in ACS patients (P = 1.2 × 10-15 and P = 1.0 × 10-5 respectively), but the healthy cohort showed no association with IL-10 levels (P>0.05). In the ACS patients, the O antigen was also associated with an increased risk of cardiovascular death, all causes of death, and recurrent myocardial infarction (odds ratio [OR] = 1.24-1.29, P = 0.029-0.00067).
  
  
  CONCLUSIONS
  Our results suggest that the ABO antigens play important roles, not only for the immunological response in ACS patients, but also for the outcome of the disease.
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Johansson
authors.affiliation: Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.|Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Alfredsson
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Niclas
authors.initials: N
authors.lastname: Eriksson
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.|Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.|Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
mesh_terms: D000017:ABO Blood-Group System / Q000097:blood / Q000235:genetics*; D054058:Acute Coronary Syndrome / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013925:Thromboplastin / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D000017:ABO Blood-Group System; C508609:IL10 protein, human; D014841:von Willebrand Factor; D016753:Interleukin-10; D013925:Thromboplastin