High Risk for Hyperlipidemia and the Metabolic Syndrome after an Episode of Hypertriglyceridemia during 13-cis Retinoic Acid Therapy for Acne: A Pharmacogenetic Study

  1. Nicolas Rodondi, MD;
  2. Roger Darioli, MD;
  3. Albert-Adrien Ramelet, MD;
  4. Daniel Hohl, MD;
  5. Vincent Lenain, MD;
  6. Jean Perdrix, MD;
  7. Vincent Wietlisbach, PhD;
  8. Walter F. Riesen, PhD;
  9. Thomas Walther, MD;
  10. Laurent Medinger, MD;
  11. Pascal Nicod, MD;
  12. Béatrice Desvergne, MD, PhD; and
  13. Vincent Mooser, MD
  1. From CHUV University Hospital, University Medical Policlinic, and University of Lausanne, Lausanne; and Kantonsspital, St-Gallen, Switzerland.

    Abstract

    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 (≥ 89 mg/dL) (hyperresponders) and 100 persons in whom triglyceride levels changed 0.1 mmol/L (≤ 9 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 pretreatment 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% CI, 1.6 to 13.8]), hypercholesterolemia (cholesterol level > 6.5 mmol/L [>252 mg/dL]; OR, 9.1 [CI, 1.9 to 43]), truncal obesity (waist-to-hip ratio > 0.90 [OR, 11.0 (CI, 2.0 to 59)], and hyperinsulinemia (insulin–glucose ratio > 7.2; OR, 3.0 [CI, 1.6 to 5.7]). In addition, more hyperresponders had at least one parent with hypertriglyceridemia (OR, 2.6 [CI, 1.2 to 5.7]) or a ratio of total to high-density lipoprotein cholesterol that exceeded 4.0 (OR, 3.5 [CI, 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.

    Article and Author Information

    • Acknowledgments: The authors thank the study participants and dermatologists Drs. P. Morier, B. Vion, and A. Zurn for identifying patients with acne. They also thank Letizia Accordino, Yacine Ali-Yahia, Einard Castillo, Gilda Crespell, Marianne Darioli, and Monique Devaud for technical help; Juan Ruiz for providing the methods to examine the PPAR-γ Pro12Ala polymorphism; and Françoise Grange, Jacques-Antoine Haefliger, Claude Pichard, Philippe Sudre, Gérard Waeber, and Walter Wahli for helpful discussions.

    • Grant Support: By Swiss National Foundation for Scientific Research, (32-44471.95 [Dr. Mooser] and 31-5113.98 [Dr. Desvergne]); the Octave Botnar and Placide Nicod Foundation; the Michel Tossizza Foundation; and Multidisciplinary Priority Project, Lausanne University.

    • Requests for Single Reprints: Vincent Mooser, MD, Department of Medicine, CHUV University Hospital, CH-1011 Lausanne, Switzerland; e-mail, vincent.mooser{at}chuv.hospvd.ch.

    • Current Author Addresses: Drs. Rodondi, Lenain, Medinger, Nicod, and Mooser: Department of Internal Medicine, CHUV University Hospital, CH-1011 Lausanne, Switzerland.

    • Drs. Darioli and Perdrix: University Medical Policlinic, Rue César-Roux 9, CH-1005 Lausanne, Switzerland.

    • Dr. Ramelet: Place Benjamin-Constant 2, CH-1003 Lausanne, Switzerland.

    • Dr. Hohl: Division of Dermatology, Beaumont 13, CHUV University Hospital, CH-1011 Lausanne, Switzerland.

    • Dr. Riesen: Clinical Chemistry Laboratory, Kantonsspital, CH-9007 St-Gallen, Switzerland.

    • Drs. Walther, Medinger, and Desvergne: Institute of Animal Biology, University of Lausanne/Dorigny, CH-1015 Lausanne, Switzerland.

    • Dr. Wietlisbach: Institute for Social and Preventive Medicine, University of Lausanne, Rue du Bugnon 13, CH-1011 Lausanne, Switzerland.

    • Author Contributions: Conception and design: N. Rodondi, R. Darioli, A-A. Ramelet, D. Hohl, B. Desvergne, V. Mooser.

    • Analysis and interpretation of the data: N. Rodondi, R. Darioli, V. Wietlisbach, B. Desvergne, V. Mooser.

    • Drafting of the article: N. Rodondi, V. Mooser.

    • Critical revision of the article for important intellectual content: N. Rodondi, R. Darioli, V. Wietlisbach, P. Nicod, B. Desvergne, V. Mooser.

    • Final approval of the article: N. Rodondi, R. Darioli, A-A. Ramelet, D. Hohl, V. Lenain, J. Perdrix, V. Wietlisbach, W.F. Riesen, T. Walther, L. Medinger, P. Nicod, B. Desvergne, V. Mooser.

    • Provision of study material or patients: N. Rodondi, R. Darioli, A-A. Ramelet, D. Hohl, V. Mooser.

    • Statistical expertise: N. Rodondi, R. Darioli, J. Perdrix, V. Wietlisbach, V. Mooser.

    • Obtaining of funding: R. Darioli, A-A. Ramelet, D. Hohl, P. Nicod, B. Desvergne, V. Mooser.

    • Administrative, technical, or logistic support: N. Rodondi, R. Darioli, A-A. Ramelet, D. Hohl, V. Lenain, W.F. Riesen, T. Walther, L. Medinger, P. Nicod, B. Desvergne, V. Mooser.

    • Collection and assembly of data: N. Rodondi, V. Mooser.

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    1. Ann Intern Med April 16, 2002 vol. 136 no. 8 582-589
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