Variation at position 162 of peroxisome proliferator-activated receptor alpha does not influence the effect of fibrates on cholesterol or triacylglycerol concentrations in hyperlipidaemic subjects.
The fibrate group of drugs are widely used to lower plasma lipid concentrations, especially in diabetic subjects. They exert their effects by activating peroxisome proliferator-activated receptor alpha (PPARalpha), which regulates the transcription of a number of genes involved in hepatic lipid metabolism. The discovery of polymorphisms in the PPARalpha gene raises the possibility that different variants could be associated with different responses to fibrate therapy. We have examined this in a random sample of 96 lipid clinic subjects who showed a wide range of response to fibrates. Of the known polymorphisms in PPARalpha, the only difference detected in this sample was the Leu/Val change at position 162. However, this change did not influence baseline plasma cholesterol or triacylglycerol concentrations, and was not associated with any difference in the effectiveness of fibrate treatment. Thus, there is no evidence that variation in the PPARalpha gene at position 162 is responsible for the differential response to fibrates in non-diabetic hyperlipidaemic subjects.
Puckey
L H
LH
Lipoprotein Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK.
Knight
B L
BL
D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics*; D001629:Bezafibrate / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood*; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011897:Random Allocation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000502:physiology; D012189:Retrospective Studies; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014280:Triglycerides / Q000097:blood*
D000960:Hypolipidemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; D002784:Cholesterol; D011345:Fenofibrate; D001629:Bezafibrate