Abstract 9591: A Novel Quantitative Trait Locus for Coronary Flow
Background: Coronary flow (CF) is fundamental for normal cardiac function but the genetic determinants of CF are uncharacterized. We examined the heritability of CF, taking into account blood pressure (BP) effects to discover new Quantitative Trait Loci (QTLs) and candidate genes for CF regulation.
Methods: We studied in vivo BP and ex vivo CF in normotensive Brown Norway (BN) rat and Spontaneously Hypertensive Rat (SHR), a model of impaired CF, and F1 and F2 progeny of these strains. In vivo BP was measured by carotid artery cannulation in anaesthetized animals. Ex vivo Langendorff perfusion measurements of CF were characterized at baseline, during coronary ligation and following cardiac reperfusion at a controlled heart rate. DNA was extracted and genotyping performed using Illumina's custom 768-plex Goldengate assay.
Results: 1) The broad sense heritability (H2) of CF was 30% at baseline indicating significant and previously unappreciated genetic regulation of CF. 2) CF exhibited no significant correlation with systolic or diastolic BP (baseline: p = 0.18, r = 0.10, n = 172; reperfusion: p = 0.30, r = 0.07, n = 172). 3) Linkage analysis revealed a highly significant CF QTL on rat chromosome 2 (LOD = 5.1), which is the first locus for CF. 4) At the CF locus adenosine monophosphate deaminase 1 (ampd1) and the adenosine A3 receptor (adora3) were identified as candidate genes and are the subject of ongoing studies.
Conclusion: Our data show that CF is a highly heritable trait and is BP-independent in our experimental model. We identified the first QTL for CF in any species and prioritized candidate genes for CF at the locus. Overall, these data provide the first insights into the genetic control of CF with implications for treatment of conditions characterized by impaired CF.
- © 2011 by American Heart Association, Inc.