Sex-specific genetic variants are associated with coronary endothelial dysfunction

Satoshi Yoshino, Rebecca Cilluffo, Megha Prasad, Patricia Best, Elizabeth J. Atkinson, Tatsuo Aoki, Julie M Cunningham, Mariza De Andrade, Lilach O Lerman, Amir Lerman

Research output: Contribution to journalArticle

16 Citations (Scopus)

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. Methods and 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.

Original languageEnglish (US)
Article numbere002544
JournalJournal of the American Heart Association
Volume5
Issue number4
DOIs
StatePublished - 2016

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Single Nucleotide Polymorphism
Blood Vessels
Atherosclerosis
Coronary Vessels
Acetylcholine
Coronary Disease
Insulin Resistance
Coronary Artery Disease
Arteries
Hormones
Inflammation
Injections

Keywords

  • Acetylcholine
  • Coronary disease
  • Endothelium
  • Genetics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Sex-specific genetic variants are associated with coronary endothelial dysfunction. / Yoshino, Satoshi; Cilluffo, Rebecca; Prasad, Megha; Best, Patricia; Atkinson, Elizabeth J.; Aoki, Tatsuo; Cunningham, Julie M; De Andrade, Mariza; Lerman, Lilach O; Lerman, Amir.

In: Journal of the American Heart Association, Vol. 5, No. 4, e002544, 2016.

Research output: Contribution to journalArticle

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AU - Yoshino, Satoshi

AU - Cilluffo, Rebecca

AU - Prasad, Megha

AU - Best, Patricia

AU - Atkinson, Elizabeth J.

AU - Aoki, Tatsuo

AU - Cunningham, Julie M

AU - De Andrade, Mariza

AU - Lerman, Lilach O

AU - Lerman, Amir

PY - 2016

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N2 - 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. Methods and 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.

AB - 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. Methods and 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.

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