title: Cytochrome P450 2C19 polymorphisms and valproic acid-induced weight gain.
abstract: OBJECTIVE
  Cytochrome P450 (CYP) 2C19 plays a role in the biotransformation of clinically relevant drugs as well as endogenous compounds, including sex hormones, which are known to be modulators of food intake and energy balance in humans. We attempted to investigate the influence of CYP2C19 polymorphisms on valproic acid (VPA)-induced weight gain.
  
  
  METHODS
  This retrospective longitudinal study included 85 VPA-treated and 93 carbamazepine (CBZ)-treated (as a reference) young patients with epilepsy. The body mass index (BMI) gap between the patient's BMI and the cutoff value for being overweight was calculated in each patient during the follow-up period. The longitudinal associations of the CYP2C19 genotype with the BMI gap and risk for becoming overweight during VPA or CBZ therapy were examined retrospectively using the generalized estimating equations approach and the Kaplan-Meier method.
  
  
  RESULTS
  During the follow-up period, the values of the BMI gap were significantly greater (P = 0.002 or P = 0.005) and the cumulative incidence of becoming overweight tended to be higher (P = 0.032) in the VPA-treated female patients with one or two loss-of-function CYP2C19 alleles than in the females without the loss-of-function CYP2C19 alleles. No associations were observed among the VPA-treated male patients and CBZ-treated male and female patients (P > 0.05).
  
  
  CONCLUSIONS
  This is the first report to show a relationship between the CYP2C19 polymorphism and VPA-induced weight gain in female patients with epilepsy. Further investigations are needed to verify these findings.
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Noai
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Soraoka
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kajiwara
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanamachi
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Oniki
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.|Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Kumamoto Saishunso National Hospital, Koshi, Japan.|Kumamoto Ezuko Ryoiku Iryo Center, Kumamoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ishitsu
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.|Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Saruwatari
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D015992:Body Mass Index; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D050177:Overweight / Q000139:chemically induced / Q000453:epidemiology; D011110:Polymorphism, Genetic / Q000235:genetics; D012189:Retrospective Studies; D012737:Sex Factors; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19
keywords: CYP2C19; epilepsy; genotype; overweight; pharmacogenetics