TY - JOUR
T1 - Sex-specific genetic variants are associated with coronary endothelial dysfunction
AU - Yoshino, Satoshi
AU - Cilluffo, Rebecca
AU - Prasad, Megha
AU - Best, Patricia J.M.
AU - Atkinson, Elizabeth J.
AU - Aoki, Tatsuo
AU - Cunningham, Julie M.
AU - de Andrade, Mariza
AU - Lerman, Lilach O.
AU - Lerman, Amir
N1 - Publisher Copyright:
© 2016 The Authors.
PY - 2016/4/1
Y1 - 2016/4/1
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.
KW - Acetylcholine
KW - Coronary disease
KW - Endothelium
KW - Genetics
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U2 - 10.1161/JAHA.115.002544
DO - 10.1161/JAHA.115.002544
M3 - Article
C2 - 27091178
AN - SCOPUS:84995680595
SN - 2047-9980
VL - 5
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 4
M1 - e002544
ER -