Real-world pharmacogenomics-guided antihypertensive treatment response in clinical practice underrepresented population: implications for precision prescribing and medication safety.

CYP3A5

CYP3A5 and ADD1 variants modulating response to calcium channel blockers and to diuretics respectively.

This single-centre retrospective cohort analysed 1,247 hypertensive patients starting antihypertensive monotherapy in Peshawar, Pakistan, between January 2023 and August 2025, with at least 12 months of follow-up. Five variants were genotyped by TaqMan assay: CYP3A5 rs776746, ADD1 rs4961, NEDD4L rs4149601, ADRB1 rs1801253 and ACE rs4340. The CYP3A5 non-expressor genotype was associated with better calcium channel blocker response (systolic drop 23.96 vs 19.78 mmHg; p = 9.7 × 10-5) and the ADD1 GG genotype with better diuretic response (24.02 vs 17.66 mmHg; p = 1.7 × 10-6), both surviving Bonferroni correction. However, four of five variants deviated from Hardy-Weinberg equilibrium, and in multivariable logistic regression the favourable genotypes remained non-significant trends only.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The main value of this work is that it covers a South Asian population rarely represented in pharmacogenetic studies, but Hardy-Weinberg disequilibrium in four of five variants signals a genotyping-quality or population-stratification problem that weakens every reported association. The authors say so themselves: these results are hypothesis-generating and do not justify selecting an antihypertensive on genotype. Read it as an argument for funding pharmacogenetic cohorts outside European populations, not as bedside-ready data.

Analysis by Dr Thibaut Benquey