{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T01:46:03Z","timestamp":1789782363988,"version":"4.0.1"},"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Research Programme for Universities (NRPU), HEC","award":["17231"],"award-info":[{"award-number":["17231"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Hypertension affects over 1.28 billion individuals worldwide, yet response variability to calcium channel blockers (CCBs) like amlodipine remains a challenge. While pharmacogenomic studies have implicated genetic polymorphisms in treatment outcomes, the combined effects of multiple variants remain unclear. This study investigates the influence of <jats:italic>CACNA1D<\/jats:italic> (rs3774426), <jats:italic>CACNA1C<\/jats:italic> (rs2239050, rs7311382), and <jats:italic>TRIB3<\/jats:italic> (rs2295490) variants, individually and in combination, on the antihypertensive response to amlodipine. A total of 133 hypertensive patients from Khyber Pakhtunkhwa, Pakistan, receiving amlodipine monotherapy were genotyped using ARMS-PCR and Sanger sequencing. Blood pressure response was defined as post-treatment systolic blood pressure (SBP) \u2264140 mmHg and diastolic blood pressure (DBP) \u226490 mmHg. Statistical analyses were adjusted for age, gender, BMI, dose, family history of HTN and dietary habits. The <jats:italic>CACNA1D<\/jats:italic> rs3774426 TT genotype was significantly associated with non-response in 35 patients, showing higher SBP than the CC genotype (n\u2009=\u200969). Conversely, the <jats:italic>CACNA1C<\/jats:italic> rs2239050 GG genotype (n\u2009=\u200967) was linked to improved SBP and DBP control compared to the CC genotype (n\u2009=\u200925). Combined genotype models (<jats:italic>CACNA1D<\/jats:italic>\u2013<jats:italic>CACNA1C<\/jats:italic> and <jats:italic>CACNA1D<\/jats:italic>\u2013<jats:italic>CACNA1C<\/jats:italic>\u2013<jats:italic>TRIB3<\/jats:italic>) showed strong unadjusted associations but lost significance after adjustment. These findings highlight the role of <jats:italic>CACNA1D<\/jats:italic> rs3774426 in predicting amlodipine non-response and demonstrate the potential of genetic screening for optimizing antihypertensive therapy. Integrating pharmacogenomics into clinical practice could enhance personalized treatment strategies, improving outcomes in hypertensive patients.<\/jats:p>","DOI":"10.1371\/journal.pone.0329263","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T17:27:38Z","timestamp":1754069258000},"page":"e0329263","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacogenomic insights into amlodipine response: the role of CACNA1D, CACNA1C, and TRIB3 variants in hypertensive patients"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2325-9609","authenticated-orcid":true,"given":"Wahby M.","family":"Babaresh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7932-9498","authenticated-orcid":true,"family":"Zakiullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3660-9225","authenticated-orcid":true,"given":"Sohaib Ahmad","family":"Sohail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alija","family":"Baig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malik","family":"Faisal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiman","family":"Begum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2309-6619","authenticated-orcid":true,"given":"Haseenullah","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zia","family":"Ul Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Ijaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Muhammad Mukarram","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aftab","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"issue":"1","key":"pone.0329263.ref001","first-page":"139","article-title":"The global epidemiology of hypertension Katherine","volume":"176","author":"K Mills","year":"2016","journal-title":"Physiol Behav"},{"key":"pone.0329263.ref002","first-page":"341","article-title":"Pharmacogenomics And Hypertension: Current Insights","volume":"12","author":"GH Oliveira-Paula","year":"2019","journal-title":"Pharmgenomics Pers Med"},{"key":"pone.0329263.ref003","unstructured":"World Health Organization. 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