To the Editor: Dr Chasman and colleagues1 recently reported the impact of genetic polymorphisms
on variability in response to pravastatin using a candidate gene approach.
While these findings are of considerable interest, their impact may be limited
from a public policy perspective. For example, while AT heterozygotes at single-nucleotide
polymorphism 12 (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase
gene) had an attenuated response to pravastatin in lowering low-density lipoprotein
(LDL) cholesterol, variant carriers represented only 6.7% of the population.
Whether it is cost-effective to genotype 15 patients initiated on statin therapy
to identify 1 patient who will have an attenuated LDL cholesterol response
must be decided from a societal perspective. The fact that even those with
an attenuated response had a 28-mg/dL (0.73-mmol/L) reduction in LDL cholesterol
further challenges the usefulness of genotype-guided therapy in this scenario.
Zineh I. Genetic Polymorphisms and Statin Therapy. JAMA. 2004;292(11):1302–1303. doi:10.1001/jama.292.11.1302-b