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To discern potential mechanisms of a genotype effect, associated SNPs were further examined for their association with change in blood pressure, circulating procollagen type III N\u2010terminal peptide (PIIINP), and left atrial area.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Results<\/jats:title><jats:p>Carriers of the rs5522 G allele in the placebo arm had a greater increase in E\/e\u2032 over the 12\u2010month course of the trial compared to noncarriers (\u03b2\u00a0=\u00a01.10; 95% confidence interval [CI]: 0.05\u20132.16; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.04). No corresponding E\/e\u2032 worsening by rs5522 genotype was observed in the spironolactone arm. None of the other genotypes were associated with change in E\/e\u2032. Compared to noncarriers, rs5522 G carriers also had a greater increase in left atrial area with placebo (\u03b2\u00a0=\u00a00.83; 95% CI: 0.17\u20131.48; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.01) and a greater reduction in diastolic blood pressure with spironolactone (\u03b2\u00a0=\u00a0\u22123.56; 95% CI: \u22126.73 to \u22120.39; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.03). Serum PIIINP levels were similar across rs5522 genotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results suggest that spironolactone attenuates progression of diastolic dysfunction associated with the <jats:italic>NR3C2<\/jats:italic> rs5522 G allele. Validation of our findings is needed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2626","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T15:10:27Z","timestamp":1632755427000},"page":"978-987","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<i>NR3C2<\/i> genotype is associated with response to spironolactone in diastolic heart failure patients from the Aldo\u2010DHF trial"],"prefix":"10.1002","volume":"41","author":[{"given":"Leanne","family":"Dumeny","sequence":"first","affiliation":[{"name":"Center for Pharmacogenomics and Precision Medicine and Department of Pharmacotherapy and Translational Research College of Pharmacy University of Florida Gainesville Florida USA"},{"name":"Genetics and Genomics Genetics Institute University of Florida Gainesville Florida 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