Comparison of the efficacy of fibrates on hypertriglyceridemic phenotypes with different genetic and clinical characteristics

Hypertriglyceridemia is a frequent and heterogeneous clinical trait, which modulates the risk of disease. Fibrates constitute an effective class of triglyceride-lowering agents. Objective To evaluate the effect of fibrates on fasting plasma triglycerides and other lipids levels in hypertriglyceridemia phenotypes with different genetic and clinical characteristics. Methods This study included 146 fasting adults: 15 with lactescent plasma and severe hypertriglyceridemia (triglyceride >= 10 mmol/l) and 131 with clear plasma and moderate hypertriglyceridemia (2 <= triglycerides < 10 mmol/l). Expost comparisons of the effect of fibrates on fasting triglycerides and other lipids were made using Student's paired two-tailed t-test. Results Response to these fibrates differed significantly across the studied hypertriglyceridemia subtypes: patients with severe hypertriglyceridemia because of lipoprotein lipase deficiency and those with moderate hypertriglyceridemia because of glycerol kinase deficiency did not respond at all, whereas patients with palmar xanthomas and severe or moderate hypertriglyceridemia because of apolipoprotein (apo) E resistance (type-III dysbetalipoproteinemia, most often associated with the apo E2 allele) responded significantly better (P < 0.001) than all other subtypes on several lipid fractions. Conclusion These results indicate that genetic factors known to contribute to the etiology and clinical expression of hypertriglyceridemia subtypes also modulate the response to triglyceride-lowering drugs. Pharmacogenetics and Genomics 20:742-747 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.