title: High risk for hyperlipidemia and the metabolic syndrome after an episode of hypertriglyceridemia during 13-cis retinoic acid therapy for acne: a pharmacogenetic study.
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.
  
  
  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.
authors.affiliation: Department of Internal Medicine, CHUV University Hospital, University Medical Policlinic, CH-1011 Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodondi
authors.forename: Roger
authors.initials: R
authors.lastname: Darioli
authors.forename: Albert-Adrien
authors.initials: AA
authors.lastname: Ramelet
authors.forename: Daniel
authors.initials: D
authors.lastname: Hohl
authors.forename: Vincent
authors.initials: V
authors.lastname: Lenain
authors.forename: Jean
authors.initials: J
authors.lastname: Perdrix
authors.forename: Vincent
authors.initials: V
authors.lastname: Wietlisbach
authors.forename: Walter F
authors.initials: WF
authors.lastname: Riesen
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
authors.forename: Laurent
authors.initials: L
authors.lastname: Medinger
authors.forename: Pascal
authors.initials: P
authors.lastname: Nicod
authors.forename: Béatrice
authors.initials: B
authors.lastname: Desvergne
authors.forename: Vincent
authors.initials: V
authors.lastname: Mooser
mesh_terms: 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
chemical_list: D001057:Apolipoproteins E; D003879:Dermatologic Agents; D007328:Insulin; D008055:Lipids; D015474:Isotretinoin