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Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay (EMSA) and DNA-affinity Precipitation Assay (DAPA)
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Genome-wide assessment for genetic variants associated with ventricular dysfunction after primary coronary artery

Amanda A Fox1, Mias Pretorius, Kuang-Yu Liu

  • 1Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. afox@partners.org

Plos One
|October 8, 2011
PubMed

Insights

Genetic variants may modestly increase risk for postoperative ventricular dysfunction (VnD) after coronary artery bypass graft (CABG) surgery. Further research in larger cohorts is needed to confirm these findings and explore underlying biological mechanisms.

Area of Science:

  • Cardiovascular Genetics
  • Genomics
  • Surgical Outcomes

Background:

  • Postoperative ventricular dysfunction (VnD) affects 9-20% of patients undergoing coronary artery bypass graft (CABG) surgery, increasing morbidity and mortality.
  • Identifying genetic factors for VnD can improve risk stratification and inform prevention strategies.

Purpose of the Study:

  • To investigate the association between genetic variants and the occurrence of in-hospital VnD following CABG surgery.
  • To identify specific single nucleotide polymorphisms (SNPs) linked to increased risk of postoperative VnD.

Main Methods:

  • A genome-wide association study (GWAS) was conducted on male patients of European ancestry undergoing isolated primary CABG.
  • VnD was defined by the need for inotropes or mechanical support post-surgery.
  • Validated SNPs were assessed in replication cohorts, followed by meta-analysis.

Main Results:

  • Over 100 SNPs showed association with VnD (P<10(-4)), with one SNP (rs17691914) reaching genome-wide significance.
  • Meta-analysis identified three SNPs (rs17691914 at 3p22.3, rs17061085 at 3p14.2, and rs12279572 at 11q23.2) modestly associated with increased risk of postoperative VnD after adjusting for clinical factors.

Conclusions:

  • No SNPs demonstrated strong risk (OR>2.1) for in-hospital VnD after CABG.
  • Three genetic loci show a modest association with postoperative VnD development.
  • Larger cohort studies are recommended to validate these loci and elucidate genetic mechanisms linking variants to VnD.
Abstract

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