https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52450 Wed 11 Oct 2023 15:02:08 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52298 Mon 09 Oct 2023 10:11:19 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39991 P = 0.013]. The G allele was associated with higher plasma serum ET-1 [least squares mean 1.59 pg/mL vs. 1.28 pg/mL; 95% confidence interval (CI) 0.10–0.53; P  = 0.005]. Patients with rs9349379-G allele had over double the odds of CMD [odds ratio (OR) 2.33, 95% CI 1.10–4.96; P  = 0.027]. Multimodality non-invasive testing confirmed the G allele was associated with linked impairments in myocardial perfusion on stress cardiac magnetic resonance imaging at 1.5 T (N = 107; GG 56%, AG 43%, AA 31%, P  = 0.042) and exercise testing (N = 87; −3.0 units in Duke Exercise Treadmill Score; −5.8 to −0.1; P  = 0.045). Endothelin-1 related vascular mechanisms were assessed ex vivo using wire myography with endothelin A receptor (ET_A) antagonists including zibotentan. Subjects with rs9349379-G allele had preserved peripheral small vessel reactivity to ET-1 with high affinity of ET_A antagonists. Zibotentan reversed ET-1-induced vasoconstriction independently of G allele status. Conclusion: We identify a novel genetic risk locus for CMD. These findings implicate ET-1 dysregulation and support the possibility of precision medicine using genetics to target oral ET_A antagonist therapy in patients with microvascular angina. Trial registration: ClinicalTrials.gov: NCT03193294.]]> Fri 15 Jul 2022 10:14:01 AEST ]]>