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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
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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
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Journal Article
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
2015
Overview
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.
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.
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).
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
ABO Blood-Group System - blood
/ ABO Blood-Group System - genetics
/ Acute Coronary Syndrome - blood
/ Acute Coronary Syndrome - genetics
/ Acute Coronary Syndrome - pathology
/ Adult
/ Aged
/ Antigens
/ Blood
/ Female
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomes
/ Humans
/ Loci
/ Male
/ Patients
/ Polymorphism, Single Nucleotide
/ Science
/ Single nucleotide polymorphisms
/ Single-nucleotide polymorphism
/ Studies
/ Tagging
