Pharmacophore an International Research Journal
Fibrates act to attenuate atherogenic dyslipidemia in type 2 diabetic patients. However an increase of serum homocysteine (tHcy) after fenofibrate treatment has been reported, compromising its cardiovascular benefit. The effect of polymorphisms in cholesteryl ester transfer protein (CETP), apolipoprotein A5 (apo A 5), and methylenetetrahydrofolate reductase (MTHFR) genes on fenofibrate treatment in type 2 diabetic patients. Patients are taking lipid lowering drugs for the first time. Polymorphisms are studied by RFLP-PCR (Restriction Fragment Length Polymorphism-Polymerase Chain Reaction). Biochemical parameters are measured by enzymatic methods. CETP activity is determined by exogenous way. Total plasma homocysteine levels (tHcy) were assessed by capillary gas chromatography-mass spectrometry method. After fenofibrate use, a significant decrease of Triglyceride (TG) level (29 %) and a decrease of total cholesterol (TC) (p = 0.081) and CETP activity (p = 0.089) were noted. However, the High Density Lipoprotein-Cholesterol (HDL-C) concentration has increased (p= 0.081) while Low Density Lipoprotein-Cholesterol (LDL-C) levels did not vary. Moreover, the prevalence of hyperhomocysteinemia rose to 100 %. Both apo A5 TT and TC carriers showed significant decrease of TG levels. Whereas the HDL-C variation is better in TT genotype (23.5 % vs -1.3 % for TT and TC respectively; p = 0.062). The decrease of TG levels after fenofibrate treatment is more important in B1B1 than in B2B2 genotype of CETP polymorphism. Only B1B1 homozygous showed a decrease of CETP activity and an increase of HDL-C. After fenofibrate use, the increase of tHcy levels was more important in MTHFR T carriers than in CC homozygous (39.97 ± 14.77 vs. 28.02 ± 8.59 μmol/l, respectively). The TT apo A5, B1B1 CETP and CC MTHFR carriers benefit the most from lipid lowering fenofibrate treatment. Pharmacogenomic studies have a great economic and health interest for a better treatment of type 2 diabetic patients.
