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

Nicolas Rodondi, MD; Roger Darioli, MD; Albert-Adrien Ramelet, MD; Daniel Hohl, MD; Vincent Lenain, MD; Jean Perdrix, MD; Vincent Wietlisbach, PhD; Walter F. Riesen, PhD; Thomas Walther, MD; Laurent Medinger, MD; Pascal Nicod, MD; Béatrice Desvergne, MD, PhD; and Vincent Mooser, MD
[+] Article and Author Information

From CHUV University Hospital, University Medical Policlinic, and University of Lausanne, Lausanne; and Kantonsspital, St-Gallen, Switzerland.


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@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.


Ann Intern Med. 2002;136(8):582-589. doi:10.7326/0003-4819-136-8-200204160-00007
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Our study shows that young adults who previously had developed elevated plasma triglyceride levels during isotretinoin therapy for acne are at increased risk for future truncal obesity, hypercholesterolemia, hypertriglyceridemia, hyperinsulinemia, and hyperuricemia, all of which are markers of the metabolic syndrome (68). Hyperresponders were more likely than nonresponders to have one or two dyslipidemic parents. Finally, the lipid response to isotretinoin therapy was closely associated with the apoE gene. Taken together, these data are consistent with the hypothesis that isotretinoin exacerbates the phenotypic expression of a latent, partly familial and genetic predisposition to hyperlipidemia and the metabolic syndrome in hyperresponders. Conversely, nonresponders may be protected against these conditions.

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Figures

Grahic Jump Location
Figure 1.
Flow chart of the study.

To convert mmol/L to mg/dL, divide by 0.0113.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Risk for metabolic disorders according to the previous lipid response to isotretinoin therapy for acne in 102 hyperresponders and 100 nonresponders.apoE

Odds ratios were calculated by using logistic regression analysis after adjustment for age, sex, genotype, and dosage of isotretinoin. BMI = body mass index; CAD = coronary artery disease; HDL = high-density lipoprotein; LDL = low-density lipoprotein. To convert triglyceride values to mg/dL, divide by 0.0113; to convert total, HDL, and LDL cholesterol values to mg/dL, divide by 0.0259.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Risk for metabolic disorders in parents of 71 hyperresponders and 60 nonresponders.leftright

Logistic regression analysis was used to calculate the risk for having one ( ) or two ( ) parents with metabolic disorders. BMI = body mass index; CAD = coronary artery disease; HDL = high-density lipoprotein; LDL = low-density lipoprotein. To convert triglyceride values to mg/dL, divide by 0.0113; to convert total, HDL, and LDL cholesterol values to mg/dL, divide by 0.0259.

Grahic Jump Location

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Summary for Patients

An Unusual “Side Effect” of an Acne Drug

The summary below is from the full report titled “High Risk for Hyperlipidemia and the Metabolic Syndrome after an Episode of Hypertriglyceridemia during 13-cis Retinoic Acid Therapy for Acne: A Pharmacogenetic Study.” It is in the 16 April 2002 issue of Annals of Internal Medicine (volume 136, pages 582-589). The authors are N Rodondi, R Darioli, A-A Ramelet, D Hohl, V Lenain, J Perdrix, V Wietlisbach, WF Riesen, T Walther, L Medinger, P Nicod, B Desvergne, and V Mooser.

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