---
title: "Pharmacogenomics-guided antihypertensive response in an underrepresented South Asian cohort"
id: "pubmed-42722881"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42722881"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42722881/"
doi: "10.1007/s00228-026-04176-7"
published_at: "2026-09-11T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Pharmacogenomics-guided antihypertensive response in an underrepresented South Asian cohort
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42722881
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42722881/)
- **DOI:** [10.1007/s00228-026-04176-7](https://doi.org/10.1007%2Fs00228-026-04176-7)
- **Published At:** 2026-09-11T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This retrospective EHR-based cohort study evaluated pharmacogenomics associations with antihypertensive response in 1,247 hypertensive adults treated at Kuwait Teaching Hospital, Peshawar, between January 2023 and August 2025. It targeted an underrepresented South Asian (Khyber Pakhtunkhwa, Pakistan) population. - Five variants were genotyped using TaqMan assays: **CYP3A5 rs776746**, **ADD1 rs4961**, **NEDD4L rs4149601**, **ADRB1 rs1801253**, and **ACE rs4340**. Inclusion required initiation of antihypertensive monotherapy and ≥12 months of EHR follow-up. - Primary outcomes were mean systolic blood pressure (SBP) reduction and achievement of target blood pressure (< 140/90 mmHg). Statistical approaches included ANOVA, multivariable logistic regression, ROC analysis, Bonferroni correction (α = 0.002) and bootstrap validation (1,000 iterations). - Baseline cohort characteristics: mean age 63.1 ± 11.5 years; 53.0% female; baseline SBP/DBP 157.1 ± 18.8 / 91.7 ± 11.1 mmHg. - Drug-class effects: **calcium channel blockers (CCBs)** delivered greater SBP reduction than other classes (22.32 ± 8.78 vs. 19.68 ± 8.67 mmHg; overall ANOVA p = 3.3 × 10-4, Bonferroni-significant). - Variant-treatment associations: **CYP3A5 rs776746 *3/*3** genotype associated with larger CCB response (23.96 ± 8.79 vs. 19.78 ± 8.17 mmHg; p = 9.7 × 10-5). **ADD1 rs4961 GG** genotype associated with larger diuretic response (24.02 ± 8.84 vs. 17.66 ± 8.69 mmHg; p = 1.7 × 10-6). Both remained significant after Bonferroni correction. - Four of five variants deviated from Hardy-Weinberg equilibrium on direct recalculation (CYP3A5 p = 0.0058; NEDD4L p = 0.0146; ADRB1 p < 0.0001; ACE p = 0.0379); only ADD1 was in equilibrium (p = 0.554). - Multivariable predictors of achieving target BP included older age (aOR 1.019), lower baseline SBP (aOR 0.915 per mmHg), and absence of diabetes (diabetes aOR 0.670). CCB therapy and favorable CYP3A5/ADD1 genotypes trended positively but were not statistically significant in adjusted models. - Model discrimination: AUC 0.847 with optimism-corrected AUC 0.841 (95% CI 0.823–0.866) after bootstrap resampling. - Authors caution that observed Hardy-Weinberg disequilibrium, potential population stratification, genotyping considerations, observational design, and lack of external validation limit immediate clinical implementation; findings are described as hypothesis-generating for precision prescribing and medication safety in this underrepresented population.
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Box 84428, Riyadh, 11671, Saudi Arabia."), [Muhammad Ilyas](https://pubmed.ncbi.nlm.nih.gov/?term=Ilyas+M&cauthor_id=42722881)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42722881/#full-view-affiliation-2 "Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN, 55455, USA. muhammadilyas01@aup.edu.pk.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42722881/#full-view-affiliation-3 "Department of Agricultural Chemistry & Biochemistry, Faculty of Nutrition Sciences, The University of Agriculture, Peshawar, 25130, Khyber Pakhtunkhwa, Pakistan. muhammadilyas01@aup.edu.pk."), [Zafar Ali Shah](https://pubmed.ncbi.nlm.nih.gov/?term=Shah+ZA&cauthor_id=42722881)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42722881/#full-view-affiliation-4 "Department of Agricultural Chemistry & Biochemistry, Faculty of Nutrition Sciences, The University of Agriculture, Peshawar, 25130, Khyber Pakhtunkhwa, Pakistan. zafarali@aup.edu.pk."), [Ammena Y Binsaleh](https://pubmed.ncbi.nlm.nih.gov/?term=Binsaleh+AY&cauthor_id=42722881)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42722881/#full-view-affiliation-1 "Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia."), [Amani S Alrossies](https://pubmed.ncbi.nlm.nih.gov/?term=Alrossies+AS&cauthor_id=42722881)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42722881/#full-view-affiliation-1 "Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia."), [Fahad A Almazyad](https://pubmed.ncbi.nlm.nih.gov/?term=Almazyad+FA&cauthor_id=42722881)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42722881/#full-view-affiliation-5 "Department of Family Medicine, King Abdullah bin Abdulaziz University Hospital, Riyadh, Saudi Arabia.") Affiliations Expand ### Affiliations * 1 Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia. * 2 Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN, 55455, USA. muhammadilyas01@aup.edu.pk. * 3 Department of Agricultural Chemistry & Biochemistry, Faculty of Nutrition Sciences, The University of Agriculture, Peshawar, 25130, Khyber Pakhtunkhwa, Pakistan. muhammadilyas01@aup.edu.pk. * 4 Department of Agricultural Chemistry & Biochemistry, Faculty of Nutrition Sciences, The University of Agriculture, Peshawar, 25130, Khyber Pakhtunkhwa, Pakistan. zafarali@aup.edu.pk. * 5 Department of Family Medicine, King Abdullah bin Abdulaziz University Hospital, Riyadh, Saudi Arabia. * PMID: **42722881** * DOI: [ 10.1007/s00228-026-04176-7 ](https://doi.org/10.1007/s00228-026-04176-7) Item in Clipboard # Real-world pharmacogenomics-guided antihypertensive treatment response in clinical practice underrepresented population: implications for precision prescribing and medication safety Nawal Alsubaie et al. Eur J Clin Pharmacol. 2026. Show details Display options Display options Format Abstract PubMed PMID Eur J Clin Pharmacol Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Eur+J+Clin+Pharmacol%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Eur+J+Clin+Pharmacol%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42722881/) . 2026 Sep 11;82(9):251. doi: 10.1007/s00228-026-04176-7. ### Authors [Nawal Alsubaie](https://pubmed.ncbi.nlm.nih.gov/?term=Alsubaie+N&cauthor_id=42722881)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42722881/#short-view-affiliation-1 "Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia."), [Muhammad Ilyas](https://pubmed.ncbi.nlm.nih.gov/?term=Ilyas+M&cauthor_id=42722881)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42722881/#short-view-affiliation-2 "Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN, 55455, USA. muhammadilyas01@aup.edu.pk.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42722881/#short-view-affiliation-3 "Department of Agricultural Chemistry & Biochemistry, Faculty of Nutrition Sciences, The University of Agriculture, Peshawar, 25130, Khyber Pakhtunkhwa, Pakistan. muhammadilyas01@aup.edu.pk."), [Zafar Ali Shah](https://pubmed.ncbi.nlm.nih.gov/?term=Shah+ZA&cauthor_id=42722881)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42722881/#short-view-affiliation-4 "Department of Agricultural Chemistry & Biochemistry, Faculty of Nutrition Sciences, The University of Agriculture, Peshawar, 25130, Khyber Pakhtunkhwa, Pakistan. zafarali@aup.edu.pk."), [Ammena Y Binsaleh](https://pubmed.ncbi.nlm.nih.gov/?term=Binsaleh+AY&cauthor_id=42722881)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42722881/#short-view-affiliation-1 "Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia."), [Amani S Alrossies](https://pubmed.ncbi.nlm.nih.gov/?term=Alrossies+AS&cauthor_id=42722881)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42722881/#short-view-affiliation-1 "Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia."), [Fahad A Almazyad](https://pubmed.ncbi.nlm.nih.gov/?term=Almazyad+FA&cauthor_id=42722881)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42722881/#short-view-affiliation-5 "Department of Family Medicine, King Abdullah bin Abdulaziz University Hospital, Riyadh, Saudi Arabia.") ### Affiliations * 1 Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia. * 2 Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN, 55455, USA. muhammadilyas01@aup.edu.pk. * 3 Department of Agricultural Chemistry & Biochemistry, Faculty of Nutrition Sciences, The University of Agriculture, Peshawar, 25130, Khyber Pakhtunkhwa, Pakistan. muhammadilyas01@aup.edu.pk. * 4 Department of Agricultural Chemistry & Biochemistry, Faculty of Nutrition Sciences, The University of Agriculture, Peshawar, 25130, Khyber Pakhtunkhwa, Pakistan. zafarali@aup.edu.pk. * 5 Department of Family Medicine, King Abdullah bin Abdulaziz University Hospital, Riyadh, Saudi Arabia. * PMID: **42722881** * DOI: [ 10.1007/s00228-026-04176-7 ](https://doi.org/10.1007/s00228-026-04176-7) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Pharmacogenomics-guided therapy is a promising approach for optimizing antihypertensive treatment response; however, robust real-world data from South Asian and particularly Pakistani populations remain scarce. Understanding genotype-drug response relationships in this underrepresented population is essential to inform context-specific precision prescribing strategies. **Objective:** To evaluate associations between pharmacogenomics variants and antihypertensive therapy response using electronic health record (EHR) data from Khyber Pakhtunkhwa (KPK) patients, and to assess the incremental predictive value and practical limitations of genotype-based stratification in routine clinical care. **Methods:** This retrospective cohort study analyzed 1,247 hypertensive patients treated at Kuwait Teaching Hospital (KTH), Peshawar, between January 2023 and August 2025. Hypertensive adults initiating antihypertensive monotherapy with at least 12 months of EHR follow-up and available genotyping results were included to minimize misclassification of treatment response. Five pharmacogenomics variants (CYP3A5 rs776746, ADD1 rs4961, NEDD4L rs4149601, ADRB1 rs1801253, and ACE rs4340) were genotyped using TaqMan assays. Primary outcomes were systolic blood pressure (SBP) reduction and target BP achievement (< 140/90 mmHg), analyzed using ANOVA, multivariable logistic regression, and receiver operating characteristic (ROC) curve analysis. Multiple testing was addressed using a Bonferroni-corrected significance threshold (α = 0.002) for variant-drug class associations, and model discrimination was internally validated using bootstrap resampling (1,000 iterations). **Results:** Mean patient age was 63.1 ± 11.5 years; 661 (53.0%) were female. Baseline SBP/DBP were 157.1 ± 18.8/91.7 ± 11.1 mmHg. Calcium channel blockers (CCBs) produced greater SBP reduction than other classes (22.32 ± 8.78 vs. 19.68 ± 8.67 mmHg, t = 4.43, p = 1.0 × 10- 5; overall drug-class ANOVA F = 5.27, p = 3.3 × 10- 4, Bonferroni-significant). The CYP3A5 rs776746 *3/*3 genotype was associated with enhanced CCB response (23.96 ± 8.79 vs. 19.78 ± 8.17 mmHg, p = 9.7 × 10- 5), and the ADD1 rs4961 GG genotype with superior diuretic response (24.02 ± 8.84 vs. 17.66 ± 8.69 mmHg, p = 1.7 × 10- 6); both associations remained significant after Bonferroni correction. On direct recalculation from raw genotype counts, four of five variants deviated from Hardy-Weinberg equilibrium (CYP3A5 p = 0.0058, NEDD4L p = 0.0146, ADRB1 p < 0.0001, ACE p = 0.0379), while ADD1 remained in equilibrium (p = 0.554). In multivariable logistic regression, older age (aOR = 1.019, 95% CI 1.007-1.031), lower baseline SBP (aOR = 0.915, 95% CI 0.906-0.925), and absence of diabetes (aOR = 0.670 for diabetes, 95% CI 0.499-0.901) were independent predictors of target BP achievement; CCB therapy (aOR = 1.362, 95% CI 0.975-1.902) and favorable CYP3A5/ADD1 genotypes (aOR 1.14 each) showed positive but non-significant trends. The model achieved an AUC of 0.847, with a bootstrap-derived optimism-corrected AUC of 0.841 (95% CI 0.823-0.866). **Conclusions:** Real-world EHR data from Khyber Pakhtunkhwa reveal significant genotype-treatment response associations for CCB and diuretic therapy in an underrepresented South Asian population. However, the extensive Hardy-Weinberg disequilibrium observed across four of five variants indicates that population stratification and/or genotyping considerations must be more fully accounted for, and together with the observational design and lack of external validation, these findings should be regarded as hypothesis-generating rather than sufficient grounds for routine clinical implementation of pharmacogenomics-guided antihypertensive therapy. **Keywords:** Antihypertensive therapy; Electronic health records; Genetic variants; Hypertension; Pharmacogenomics; Precision medicine. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Ethics approval and consent to participate: The Institutional Ethics Review Board of Kuwait Teaching Hospital, Peshawar, approved this study (Approval No: KTH-ERB-2023-045, January 2023), with a waiver of individual informed consent for retrospective analysis, in accordance with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. ## References 1. 1. Jafar TH, Haaland BA, Rahman A et al (2013) Non-communicable diseases and injuries in Pakistan: strategic priorities. Lancet 381:2281–2290 - [DOI](https://doi.org/10.1016/s0140-6736\(13\)60646-7) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/23684257/) 2. 1. Khatib R, McKee M, Shannon H et al (2016) Availability and affordability of cardiovascular disease medicines and their effect on use in high-income, middle-income, and low-income countries: an analysis of the PURE study data. Lancet 387:61–69 - [DOI](https://doi.org/10.1016/s0140-6736\(15\)00469-9) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/26498706/) 3. 1. Saleem F, Hassali AA, Shafie AA (2010) Hypertension in Pakistan: time to take some serious action. Br J Gen Pract 60:449–450 - [DOI](https://doi.org/10.3399/bjgp10x502182) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/20529498/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/2880743/) 4. 1. Johnson JA, Cavallari LH (2013) Pharmacogenetics and cardiovascular disease-implications for personalized medicine. Pharmacol Rev 65:987–1009 - [DOI](https://doi.org/10.1124/pr.112.007252) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/23686351/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/3698938/) 5. 1. Turner RM, Pirmohamed M (2014) Cardiovascular pharmacogenomics: expectations and practical benefits. Clin Pharmacol Ther 95:281–293 - [DOI](https://doi.org/10.1038/clpt.2013.234) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/24322971/) Show all 28 references ## MeSH terms * Aged Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Aged%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Aged) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42722881/) * Antihypertensive Agents* / adverse effects Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Antihypertensive+Agents%2Fadverse+effects%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Antihypertensive+Agents) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42722881/) * Antihypertensive Agents* / therapeutic use Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Antihypertensive+Agents%2Ftherapeutic+use%22%5B
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