Genetic profiling versus drug rotation in the optimisation of antihypertensive treatment.
There is a greater choice of drug classes for hypertension than most other diseases, increasing paradoxically the difficulty of finding the right drug for individual patients. Systematic drug rotation studies have shown that the rank order of response to different drugs varies substantially among patients. However, two broad patterns of response emerge, named after the initials of the major drug classes. The AB pattern is seen in Type 1 (high-renin) hypertensives. These are younger Caucasians who respond best to angiotensin-converting enzyme (ACE) inhibitors, angiotensin blockers and beta-blockers. The CD pattern is seen in Type 2 (low-renin) patients. These are Afro-Caribbeans and older Caucasians, who respond best to calcium blockers and diuretics. This relative homogeneity of phenotype at each age group contrasts with a large heterogeneity of genotype on recent genome-wide scans, and suggests that most hypertension is due to interaction among multiple minor genetic variants. Genotype is unlikely therefore to be useful in selecting treatment for most patients. The exception is patients who have the atypical phenotype for their age, illustrated by the rare Na+ dependent monogenic syndromes of the young.
Mackenzie
Isla S
IS
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital.
Brown
Morris J
MJ
D004232:Diuretics / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D018740:Genetic Heterogeneity; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics*; D012083:Renin / Q000097:blood; D013148:Spironolactone / Q000627:therapeutic use; D016896:Treatment Outcome
D004232:Diuretics; D013148:Spironolactone; D012083:Renin