TY - JOUR
T1 - Single nucleotide polymorphisms associated with abnormal coronary microvascular function
AU - Yoshino, Satoshi
AU - Cilluffo, Rebecca
AU - Best, Patricia J.M.
AU - Atkinson, Elizabeth J.
AU - Aoki, Tatsuo
AU - Cunningham, Julie M.
AU - De Andrade, Mariza
AU - Choi, Byoung Joo
AU - Lerman, Lilach O.
AU - Lerman, Amir
PY - 2014/6
Y1 - 2014/6
N2 - BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most common source of genetic variation. Although microvascular pathology is associated with cardiovascular events, genetic phenotypes causing microvascular disease remain largely unknown. This study identifies sex-specific SNPs associated with coronary microvascular dysfunction. METHODS AND RESULTS: Six hundred and forty-three patients without significant obstructive coronary heart disease were enrolled, referred for cardiac catheterization, and underwent invasive coronary microcirculatory assessment. Patient data were collected from 1529 autosomal SNPs and seven X chromosome SNPs, which were selected to represent the variability from 76 candidate genes with published associations with coronary vasoreactivity, angiogenesis, inflammation, vascular calcification, atherosclerosis risk factors, female hormones, blood coagulation, or coronary heart disease. Coronary flow reserve (CFR) was assessed by an intracoronary injection of adenosine. Patients were categorized according to a CFR above or below 2.5 and were stratified by sex. After adjusting for age, sex, and BMI, this study shows that SNPs within VEGFA and CDKN2B-AS1 are associated with abnormal CFR (P<0.005). SNPs within MYH15, VEGFA, and NT5E are associated with abnormal CFR in men. No SNPs were associated with abnormal CFR in women. CONCLUSION: Genetic variations within defined regions of VEGFA and CDKN2B-AS1 genes are associated with coronary microvascular dysfunction. Furthermore, sex-specific allelic variants within MYH15, VEGFA, and NT5E are associated with an increased risk of coronary microvascular dysfunction in men.
AB - BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most common source of genetic variation. Although microvascular pathology is associated with cardiovascular events, genetic phenotypes causing microvascular disease remain largely unknown. This study identifies sex-specific SNPs associated with coronary microvascular dysfunction. METHODS AND RESULTS: Six hundred and forty-three patients without significant obstructive coronary heart disease were enrolled, referred for cardiac catheterization, and underwent invasive coronary microcirculatory assessment. Patient data were collected from 1529 autosomal SNPs and seven X chromosome SNPs, which were selected to represent the variability from 76 candidate genes with published associations with coronary vasoreactivity, angiogenesis, inflammation, vascular calcification, atherosclerosis risk factors, female hormones, blood coagulation, or coronary heart disease. Coronary flow reserve (CFR) was assessed by an intracoronary injection of adenosine. Patients were categorized according to a CFR above or below 2.5 and were stratified by sex. After adjusting for age, sex, and BMI, this study shows that SNPs within VEGFA and CDKN2B-AS1 are associated with abnormal CFR (P<0.005). SNPs within MYH15, VEGFA, and NT5E are associated with abnormal CFR in men. No SNPs were associated with abnormal CFR in women. CONCLUSION: Genetic variations within defined regions of VEGFA and CDKN2B-AS1 genes are associated with coronary microvascular dysfunction. Furthermore, sex-specific allelic variants within MYH15, VEGFA, and NT5E are associated with an increased risk of coronary microvascular dysfunction in men.
KW - coronary flow reserve
KW - coronary microvascular dysfunction
KW - single nucleotide polymorphisms
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U2 - 10.1097/MCA.0000000000000104
DO - 10.1097/MCA.0000000000000104
M3 - Article
C2 - 24736300
AN - SCOPUS:84899980326
SN - 0954-6928
VL - 25
SP - 281
EP - 289
JO - Coronary Artery Disease
JF - Coronary Artery Disease
IS - 4
ER -