Real-world EHR data from Khyber Pakhtunkhwa reveal significant genotype-treatment response associations for CCB and diuretic therapy in an underrepresented South Asian population, but extensive Hardy-Weinberg disequilibrium across four of five variants indicates findings should be regarded as hypothesis-generating rather than sufficient grounds for routine clinical implementation.
Calcium channel blockers produced greater systolic blood pressure reduction than other antihypertensive drug classes in this Pakistani population.
The CYP3A5 rs776746 *3/*3 genotype was associated with enhanced response to calcium channel blocker therapy.
The ADD1 rs4961 GG genotype was associated with superior diuretic therapy response.
Four of five pharmacogenomic variants deviated from Hardy-Weinberg equilibrium, raising concerns about population stratification or genotyping quality.
In multivariable logistic regression, older age, lower baseline SBP, and absence of diabetes were independent predictors of target blood pressure achievement, while pharmacogenomic genotypes showed only non-significant trends.
The multivariable model predicting target blood pressure achievement demonstrated good discrimination, validated through bootstrap resampling.
The study population consisted of hypertensive adults from Khyber Pakhtunkhwa, Pakistan, a population underrepresented in pharmacogenomics research.
This research suggests that certain genetic variants can influence how well patients respond to different blood pressure medications, based on data from over 1,200 hypertensive patients in the Khyber Pakhtunkhwa region of Pakistan — a population rarely included in pharmacogenomics studies. Specifically, patients with a particular variant in the CYP3A5 gene appeared to respond better to calcium channel blockers (a common type of blood pressure medication), and those with a specific ADD1 gene variant responded better to diuretics (water pills). Calcium channel blockers also showed the greatest overall blood pressure reduction compared to other drug classes. However, the strongest predictors of whether a patient reached their blood pressure goal were non-genetic factors: older age, lower starting blood pressure, and not having diabetes. A notable concern in the study was that four out of five genetic variants tested did not follow expected patterns of genetic distribution in this population (a statistical property called Hardy-Weinberg equilibrium). This could mean that genotyping errors occurred, or that the population has unique genetic structure — either of which could affect the reliability of the genetic findings. Additionally, favorable genetic profiles added only small, statistically non-significant advantages in predicting blood pressure control when all factors were considered together. This research suggests that tailoring antihypertensive treatment based on a patient's genetic profile may eventually be beneficial in South Asian populations, but the findings are preliminary. The authors caution that the study's observational design, potential genotyping issues, and lack of external validation mean these results should be considered hypothesis-generating rather than a basis for changing clinical practice. Future studies with larger, more diverse populations and rigorous genotyping quality controls will be needed to determine whether pharmacogenomics-guided prescribing can meaningfully improve blood pressure treatment in this and similar populations.
Alsubaie N, Ilyas M, Shah Z, Binsaleh A, Alrossies A, Almazyad F. (2026). Real-world pharmacogenomics-guided antihypertensive treatment response in clinical practice underrepresented population: implications for precision prescribing and medication safety.. European journal of clinical pharmacology. https://doi.org/10.1007/s00228-026-04176-7