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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. 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.

SUBMITTER: Yoshino S

PROVIDER: S-EPMC4859270 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Sex-Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction.

Yoshino Satoshi S Cilluffo Rebecca R Prasad Megha M Best Patricia J M PJ Atkinson Elizabeth J EJ Aoki Tatsuo T Cunningham Julie M JM de Andrade Mariza M Lerman Lilach O LO Lerman Amir A

Journal of the American Heart Association 20160418 4

<h4>Background</h4>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.<h4>Methods and results</h4>Six hundred forty-three subjects without significant obstructive coronary artery disease underwent invasive coronary endothelial funct ...[more]

PMID: 27091178

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Project description:Background and objectivesImportant sex differences exist in tau pathology along the Alzheimer disease (AD) continuum, with women showing enhanced tau deposition compared with men, especially during the mild cognitive impairment (MCI) phase. This study aims to identify specific genetic variants associated with sex differences in regional tau aggregation, as measured with PET.MethodsFour hundred ninety-three participants (women, n = 246; men, n = 247) who self-identified as White from the AD Neuroimaging Initiative study, with genotyping data and 18F-Flortaucipir tau PET data, were included irrespective of clinical diagnosis (cognitively normal [CN], MCI, and AD). We focused on the genetic variants within 10 genes previously shown to have sex-dependent effects on AD to reduce the burden of multiple comparisons: BIN1, MS4A6A, DNAJA2, FERMT2, APOC1, APOC1P1, FAM193B, C2orf47, TYW5, and CR1. Multivariate analysis of variance was applied to identify genetic variants associated with tau PET data in 3 regions of interests (composite regions of Braak I, Braak III/IV, and Braak V/VI stages) in women and men separately. We controlled for age, scanner manufacture, amyloid status, APOE ε4 carriership, diagnosis (CN vs MCI vs AD), and the first 10 genetic principal components to adjust for population stratification.ResultsWe identified 3 genetic loci within 3 different genes associated with tau deposits specifically in women: rs79711283 within DNAJA2, rs113357081 within FERMT2, and rs74614106 within TYW5. In men, we also identified 3 loci within CR1 associated with tau deposits: rs115096248, rs113698814, and rs78150633.DiscussionOur findings revealed sex-specific genetic variants associated with tau deposition independent of APOE ε4, amyloid status, and clinical diagnosis. These results provide potential molecular targets for understanding the mechanism of sex-specific tau aggregation and developing sex-specific gene-guided precision prevention or therapeutic interventions for AD.

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Sex-Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction.

Publications

Sex-Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction.

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