{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T20:05:45Z","timestamp":1785614745933,"version":"3.56.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> The genetic factors in assessing therapeutic efficacy and predicting antihypertensive drug response are unclear. Therefore, this study aims to identify the associations between variants and antihypertensive drug response.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A longitudinal study including 1837 hypertensive patients was conducted in Northern China and followed up for a median 2.24\u00a0years. The associations of 11 candidate variants with blood pressure changes in response to antihypertensive drugs and with the risk of cardiovascular events during the follow-up were examined. The dual-luciferase assay was carried out to assess the effect of genetic variants on gene transcriptional activity.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The variant rs11039149A&amp;gt;G in the promoter of nuclear receptor subfamily 1 group H member 3 (<jats:italic>NR1H3<\/jats:italic>) was associated with the change in systolic blood pressure (\u0394SBP) in response to calcium channel blockers (CCBs) monotherapy. Patients carrying rs11039149AG genotype showed a significant increase of systolic blood pressure (SBP) at follow-up compared with AA carriers, and the difference of \u0394SBP between AG and AA carriers was 5.94\u00a0mm Hg (95%CI: 2.09\u20139.78, <jats:italic>p<\/jats:italic> = 0.002). In 1,184 patients with CCBs therapy, SBP levels decreased in AA carriers, but increased in AG carriers, the difference of \u0394SBP between AG and AA carriers was 8.04\u00a0mm Hg (95%CI: 3.28\u201312.81, <jats:italic>p<\/jats:italic> = 0.001). Further analysis in 359 patients with CCBs monotherapy, the difference of \u0394SBP between AG and AA carriers was 15.25\u00a0mm Hg (95%CI: 6.48\u201324.02, <jats:italic>p<\/jats:italic> = 0.001). However, there was no significant difference in \u0394SBP between AG and AA carriers with CCBs multitherapy. The rs11039149A&amp;gt;G was not associated with the cardiovascular events incidence during the follow-up. Additionally, transcriptional factor forkhead box C1 (<jats:italic>FOXC1<\/jats:italic>) bound to the <jats:italic>NR1H3<\/jats:italic> promoter containing rs11039149A and significantly increased the transcriptional activity, while rs11039149 A to G change led to a loss-of-function and disabled <jats:italic>FOXC1<\/jats:italic> binding. For the other 10 variants, associations with blood pressure changes or risk of cardiovascular events were not observed.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Hypertensive patients with rs11039149AG genotype in the <jats:italic>NR1H3<\/jats:italic> gene have a significant worse SBP control in response to CCBs monotherapy compared with AA carriers. Our findings suggest that the <jats:italic>NR1H3<\/jats:italic> gene might act as a promising genetic factor to affect individual sensitivity to antihypertensive drugs.<\/jats:p>","DOI":"10.3389\/fphar.2023.1083134","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T05:04:40Z","timestamp":1678079080000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacogenetic association of the NR1H3 promoter variant with antihypertensive response among patients with hypertension: A longitudinal study"],"prefix":"10.3389","volume":"14","author":[{"given":"Yu","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutai","family":"Hui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weili","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1161\/HYPERTENSIONAHA.120.15462","article-title":"Treatment patterns and blood pressure control with initiation of combination versus monotherapy antihypertensive regimens","volume":"77","author":"An","year":"2021","journal-title":"Hypertension"},{"key":"B2","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1097\/FJC.0000000000000693","article-title":"Activation of liver X receptors by GW3965 attenuated deoxycorticosterone acetate-salt hypertension-induced cardiac functional and structural changes","volume":"74","author":"Bal","year":"2019","journal-title":"J. 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