HypertensionCohort study
Side effects in hypertension treatment: a pharmacogenomic analysis
- Genome-wide association study
- three cohorts (FinnGen, UK Biobank, Estonian Biobank)
- longitudinal medication data
Authors' conclusion
These findings extend the bradykinin hypothesis of ACEI-induced cough by implicating neurotensin-NTSR1 signalling, pinpoint CYP3A4*22 as a novel functional predictor of dCCB switching with potential for genotype-guided prescribing, and validate medication use trajectories as a framework for pharmacogenetic discovery.
Study context
- Population
- Genotyped antihypertensive medication users; first-year use trajectories (Continue, Switch, Discontinue) across five medication classes
- Participants
- >400,000 users · 3 cohorts
- Outcome
- Genetic predictors of antihypertensive medication use trajectories
- Follow-up
- First year
Main finding
As reported in the abstract
Genome-wide significant loci for switching from angiotensin-converting enzyme inhibitors (ACEI) and dihydropyridine calcium channel blockers (dCCB) to other antihypertensives
14
ACEI switching: NTSR1 rs148569146 [G301R] protective missense variant (320-fold Finnish-enriched), OR
0.49, P = 3.3 × 10-43
ACEI switching: variant near RASSF9 (rs181941187) tagging NTS, OR
0.74, P = 1.2 × 10-49
dCCB switching: CYP3A43 locus in near-complete linkage with CYP3A4*22 (rs35599367), OR
1.23, P = 6.1 × 10-10
Observational data: associations, not effects.
Further findings
ACEI-induced cough with NTSR1 G301R (drug-gene interaction)
- Reduced ACEI-induced cough risk, OR
- 0.39, P = 8.1 × 10-4
ACEI cough by polygenic risk score (PRS) for ACEI switching (independent Estonian Biobank sample)
- Two-fold ACEI cough risk in top 10% PRS vs middle 20%
Original publication
Summarised from the published abstract; every number is checked against it