[Effect of Gevilon therapy and its relation to E polymorphism]

Area of Science:

• Pharmacogenetics
• Lipid Metabolism
• Clinical Genetics

Background:

• Obesity and hyperlipoproteinemia are significant risk factors for cardiovascular disease.
• Apolipoprotein E (apoE) genotype is known to influence lipid metabolism and response to lipid-lowering therapies.
• Gemfibrozil is a commonly prescribed fibrate for managing dyslipidemia.

Purpose of the Study:

• To investigate the association between apoE allele frequencies and hyperlipoproteinemia phenotypes in obese patients.
• To evaluate the efficacy of gemfibrozil plus diet therapy based on different apoE genotypes.
• To determine if apoE genotyping can predict treatment response in hyperlipoproteinemic patients.

Main Methods:

• Clinical trial involving 81 obese, hyperlipoproteinemic patients.
• Apolipoprotein E (apoE) allele frequency estimation using polymerase chain reaction and restriction enzyme isoform genotyping.
• Analysis of lipid profiles (triglycerides) and treatment response across different apoE genotypes (E2, E3, E4) and Fredrickson phenotypes (II/A, II/B, IV+V).

Main Results:

• The relative frequencies of apoE alleles E2, E3, and E4 were 0.28, 0.61, and 0.11, respectively.
• Hypertriglyceridemia phenotypes IV+V, II/B, and II/A were dominant (44.4%, 39.5%, 16.0%).
• Gemfibrozil + diet therapy significantly reduced atherogenic lipids, with varying efficacy across genotypes (E3 > E4 > E2). Treatment was less effective in the II/A group, particularly for non-E33 genotypes, while effective across all apoE isoforms in the IV+V group.

Conclusions:

• ApoE genotype significantly impacts the efficacy of gemfibrozil + diet therapy in obese hyperlipoproteinemic patients.
• Determining apoE genotype is crucial for optimizing treatment strategies, especially in patients with Fredrickson phenotype II/B, where only the E33 genotype shows consistent efficacy across lipid parameters.
• Personalized pharmacogenetic approaches, considering apoE status, can improve lipid management and potentially reduce cardiovascular risk.