title: Sex-Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction.
abstract: BACKGROUND
  Endothelial dysfunction is an early stage of atherosclerosis. Single-nucleotide polymorphisms (SNPs) have been associated with vascular dysfunction, cardiac events, and coronary artery remodeling. We aimed to detect SNPs associated with endothelial dysfunction and determine whether these associations are sex specific.
  
  
  RESULTS
  Six hundred forty-three subjects without significant obstructive coronary artery disease underwent invasive coronary endothelial function assessment. We collected data from 1536 SNPs that had previously been associated with vasoreactivity, angiogenesis, inflammation, artery calcification, atherosclerotic risk factors, insulin resistance, hormone levels, blood coagulability, or with coronary heart disease. Coronary vascular reactivity was assessed by the percent change in coronary artery diameter ≤ -20% after an intracoronary bolus injection of acetylcholine on invasive coronary physiology study. SNPs significantly associated with coronary epicardial endothelial dysfunction were ADORA1, KCNQ1, and DNAJC4 in the whole cohort, LPA, MYBPH, ADORA3, and PON1 in women and KIF6 and NFKB1 in men (P<0.01).
  
  
  CONCLUSIONS
  We have identified several significant SNPs that are associated with an increased risk of coronary endothelial dysfunction. These associations appear to be sex specific and may explain gender-related differences in development of atherosclerosis.
authors.affiliation: Cardiovascular Medicine and Hypertension, Kagoshima University Hospital, Sakuragaoka, Kagoshima, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshino
authors.affiliation: Cardiovascular Diseases and Internal Medicine, Mayo Clinic and College of Medicine, Rochester, MN.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Cilluffo
authors.affiliation: Cardiovascular Diseases and Internal Medicine, Mayo Clinic and College of Medicine, Rochester, MN.
authors.forename: Megha
authors.initials: M
authors.lastname: Prasad
authors.affiliation: Cardiovascular Diseases and Internal Medicine, Mayo Clinic and College of Medicine, Rochester, MN.
authors.forename: Patricia J M
authors.initials: PJ
authors.lastname: Best
authors.affiliation: Biomedical Statistics and Informatics, Mayo Clinic and College of Medicine, Rochester, MN.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Atkinson
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Aoki
authors.affiliation: Genomics Shared Resource, Mayo Clinic and College of Medicine, Rochester, MN.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.affiliation: Biomedical Statistics and Informatics, Mayo Clinic and College of Medicine, Rochester, MN.
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.affiliation: Nephrology and Internal Medicine, Mayo Clinic and College of Medicine, Rochester, MN.
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.affiliation: Cardiovascular Diseases and Internal Medicine, Mayo Clinic and College of Medicine, Rochester, MN lerman.amir@mayo.edu.
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D003324:Coronary Artery Disease / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics; D003331:Coronary Vessels / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000502:physiology; D012737:Sex Factors
keywords: acetylcholine; coronary disease; endothelium; genetics