Abstract 13281: Single Nucleotide Polymorphisms Associated With Coronary Microvascular Dysfunction and Sex Differences on Genetic Influence
Background: Single nucleotide polymorphisms (SNPs) are the most common sources of genetic variations. Coronary heart disease (CHD) develops dependent of genetic predisposition and the accumulation of risk factors. Although microvascular pathology is associated with cardiovascular events, genetic analyses of microvascular disease phenotypes are rare including the report of sex-related differences. The purpose of this study was designed to assess which SNPs are associated with coronary microvascular dysfunction and to confirm whether sex difference of SNPs concerned to coronary microvascular dysfunction exists.
Methods: A total of 643 subjects without significant obstructive CHD undergoing invasive coronary microcirculatory assessment were enrolled. We have collected 1536 SNPs that are of good enough quality to analyze, and concerned to coronary vasoreactivity, angiogenesis, inflammation, cell connection, and coronary risk factors. Coronary vascular reactivity responses were studied, and coronary flow reserve (CFR) was assessed by intracoronary bolus injection of adenosine. Patients were divided into two groups according to the value of CFR. The cut-off point of CFR is 2.5. Logistic regression was run using the endpoint of CFR<2.5 to test for genetic differences after adjusting for coronary risk factors, assuming a log-additive genetic model. The patients were also subclassified into two groups according to the sex differences.
Results: Analysis of the SNPs, after adjusting for age, sex, and BMI, demonstrated that the risk alleles of KDR, VEGFA, LPA, ANGPT1, and CDKN2B-AS1 were associated with the increased risk of abnormal CFR (P<0.01). Furthermore, the risk allele of ADORA3, MYH15, KDR, ANGPT1, and CDKN2B-AS1 were associated with the increased risk of abnormal CFR in women, and the risk alleles of MYH15, KDR, VEGFC, VEGFA, NT5E, SNX14, ESR1, ANGPT1, GAS6 were associated with the increased risk of abnormal CFR in men.
Conclusions: Genetic variation within defined regions of KDR, VEGFA, LPA, ANGPT1, and CDKN2B-AS1 genes are associated with coronary microvascular dysfunction. Furthermore, there are sex-specific differences in genetic variation associated with the increased risk of coronary microvascular dysfunction.
- © 2013 by American Heart Association, Inc.