Phenotypes, genotypes and response to statin therapy.
OBJECTIVE
Response to statin treatment can vary widely from person to person as a result of inherited traits (genotype) and acquired characteristics such as obesity (phenotype). The aim of this review is to describe what is known about factors that determine a patient's response, and to offer a mechanism to explain how plasma triglyceride influences the nature and magnitude of lipid lowering on statin therapy.


RESULTS
In normotriglyceridemic individuals statins have little impact on the concentration of large VLDL, but as basal plasma triglyceride rises there is an increasing tendency for large VLDL, chylomicrons, chylomicron remnants and small, dense LDL to fall on treatment. These phenotype-dependent effects are in contrast to the phenotype-independent actions on IDL and LDL. Recent studies have also revealed that the principal mechanism by which statins lower VLDL (and LDL) in hypertriglyceridemic individuals is by stimulation of lipoprotein clearance. Individuals with low HDL-cholesterol are increasingly treated with statins. The increase in this lipoprotein affects the subfraction distribution, with a specific increase in alpha1 HDL components. Polymorphism in the promoter for the ABCG8 gene has been linked to variations in response to statins; individuals with the rarer D19H genotype exhibit a greater reduction in LDL-cholesterol. Similarly, the magnitude of the statin-induced increase in HDL-cholesterol has been linked to a polymorphism in the promoter for apolipoprotein A1.


CONCLUSIONS
Statins are administered to a wide range of individuals on an empirical basis. Investigation of the phenotype and genotype influences on treatment response will allow a more tailored use of these drugs.
Caslake
Muriel J
MJ
Department of Vascular Biochemistry, Glasgow Royal Infirmary, Glasgow, Scotland, UK. m.caslake@clin-med.gla.ac.uk
Packard
Chris J
CJ
D016632:Apolipoprotein A-I / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015228:Hypertriglyceridemia / Q000188:drug therapy*; D050356:Lipid Metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008954:Models, Biological; D010641:Phenotype; D011110:Polymorphism, Genetic; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008079:Lipoproteins, VLDL; D014280:Triglycerides