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Response to micronized fenofibrate treatment is associated with the peroxisome-proliferator-activated receptors alpha G/C intron7 polymorphism in subjects with type 2 diabetes.
823 - 829.
Objective The association between polymorphisms in candidate genes related to lipoprotein metabolism and the reduction in plasma triglyceride (TG) in response to fenofibrate treatment was evaluated in subjects with type 2 diabetes treated with micronized fenofibrate (200 mg/day) for at least 3 years in the Diabetes Atherosclerosis Intervention Study.Methods The cholesteryl ester transfer protein Taq1B, LPL S447X, hepatic lipase -514 C-->T, peroxisome-proliferator-activated receptors alpha (PPARA) L162V and G/C intron 7 polymorphisms and the apolipoprotein E2/E3/E4 alleles were genotyped using PCR and restriction enzyme digestion. Subjects were divided into high TG-responders (with >30% TG relative reduction after treatment) and low TG-responders.Results The frequency of the PPARA intron 7 G/G genotype was higher in high TG-responders than in low TG-responders (85% vs. 69%, P<0.05). There was no significant difference between the percentage of high TG-responders and low TG-responders for any of the other genetic polymorphisms examined. In stepwise logistic regression, baseline TG and only the PPARA intron 7 polymorphism among the others were selected in the model as significant predictors of TG-response (odds ratio: 3.10, 95% CI: 1.28-7.52, P=0.012 for PPARA polymorphism). With age, gender, body mass index, smoking status and HbA1c as additional factors, baseline TG (P<0.0001), intron 7 (P=0.013), body mass index (P=0.040) and LPL-S447X (P=0.084) were significant predictors of TG-response.Conclusion These results indicate that elevated baseline TG levels and PPARA gene intron 7 G/G genotype were associated with TG reduction >30% after fenofibrate treatment in patients with type 2 diabetes. (C) 2004 Lippincott Williams Wilkins.
|Title:||Response to micronized fenofibrate treatment is associated with the peroxisome-proliferator-activated receptors alpha G/C intron7 polymorphism in subjects with type 2 diabetes|
|Keywords:||fenofibrate, triglycerides response, genetic polymorphisms, PPAR, LPL, LIPC, CETP, apolipoprotein E, type 2 diabetes, DENSITY-LIPOPROTEIN CHOLESTEROL, CORONARY-ARTERY DISEASE, LIPASE GENE-MUTATIONS, APOLIPOPROTEIN-E, PPAR-ALPHA, ATHEROSCLEROSIS INTERVENTION, PROGRESSION-REGRESSION, COMMON VARIANT, PLASMA-LIPIDS, THERAPY|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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