High risk for hyperlipidemia and the metabolic syndrome after an episode of hypertriglyceridemia during 13-cis retinoic acid therapy for acne:: A pharmacogenetic study

Background: Administration of 13-cis retinoic acid (isotretinoin) for acne is occasionally accompanied by hyperlipidemia. It is not known why some persons develop this side effect. Objective: To determine whether isotretinoin triggers a familial susceptibility to hyperlipidemia and the metabolic syndrome. Design: cross-sectional comparison. Setting: University hospital in Lausanne, Switzerland. Participants: 102 persons in whom triglyceride levels increased at least 1.0 mmol/L (greater than or equal to89 mg/dL) (hyperresponders) and 100 persons in whom triglyceride levels changed 0.1 mmol/L (less than or equal to9 mg/dL) or less (nonresponders) during isotretinoin therapy for acne. Parents of 71 hyperresponders and 60 nonresponders were also evaluated. Measurements: Waist-to-hip ratio; fasting glucose, insulin, and lipid levels; and apoE genotype. Results: Hyperresponders and nonresponders had similar pre-treatment body weight and plasma lipid levels. When reevaluated approximately 4 years after completion of isotretinoin therapy, hyperresponders were more likely to have hypertriglyceridemia (triglyceride level > 2.0 mmol/L [>177 mg/dL]; odds ratio [OR], 4.8 [95% Cl, 1.6 to 13.81), hypercholesterolemia (cholesterol level > 6.5 mmol/L [>252 mg/dL]; OR, 9.1 [Cl, 1.9 to 43)), truncal obesity (waist-to-hip ratio > 0.90 [OR, 11.0 (Cl, 2.0 to 59]), and hyperinsulinemia (insulin-glucose ratio > 7.2; OR, 3.0 [Cl, 1.6 to 5.71). In addition, more hyperresponders had at least one parent with hypertriglyceridemia (OR, 2.6 [Cl, 1.2 to 5.7]) or a ratio of total to high-density lipoprotein cholesterol that exceeded 4.0 (OR, 3.5 (Cl, 1.5 to 8.0]). Lipid response to isotretinoin was closely associated with the apoE gene. Conclusion: Persons who develop hypertriglyceridemia during isotretinoin therapy for acne, as well as their parents, are at increased risk for future hyperlipidemia and the metabolic syndrome.