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.


METHODS
Cross-sectional comparison.


METHODS
University hospital in Lausanne, Switzerland.


METHODS
102 persons in whom triglyceride levels increased at least 1.0 mmol/L (> or =89 mg/dL) (hyperresponders) and 100 persons in whom triglyceride levels changed 0.1 mmol/L (< or =9 mg/dL) or less (nonresponders) during isotretinoin therapy for acne. Parents of 71 hyperresponders and 60 nonresponders were also evaluated.


METHODS
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.


CONCLUSIONS
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.
Rodondi
Nicolas
N
Department of Internal Medicine, CHUV University Hospital, University Medical Policlinic, CH-1011 Lausanne, Switzerland.
Darioli
Roger
R
Ramelet
Albert-Adrien
AA
Hohl
Daniel
D
Lenain
Vincent
V
Perdrix
Jean
J
Wietlisbach
Vincent
V
Riesen
Walter F
WF
Walther
Thomas
T
Medinger
Laurent
L
Nicod
Pascal
P
Desvergne
Béatrice
B
Mooser
Vincent
V
D000152:Acne Vulgaris / Q000097:blood / Q000188:drug therapy; D000293:Adolescent; D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics; D001835:Body Weight; D003430:Cross-Sectional Studies; D003879:Dermatologic Agents / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced* / Q000235:genetics*; D007328:Insulin / Q000097:blood; D015474:Isotretinoin / Q000009:adverse effects*; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D010597:Pharmacogenetics; D012189:Retrospective Studies; D012307:Risk Factors
D001057:Apolipoproteins E; D003879:Dermatologic Agents; D007328:Insulin; D008055:Lipids; D015474:Isotretinoin