アクティブボード・２００９年１１月
　　　　　・・・・・２００９年１１月　５日更新・・・・・

研究発表を行った学会；
・The International Symposium on Pharmacogenomics in Epilepsy
　２００９年１０月２４日（弘前）

タイトル；Clobazam-induced weight gain in children with epilepsy: The effect of cytochrome P450 2C19 genotype.
　
発表者；　濱本　愛　氏
　　　（熊本大学　大学院医学薬学研究部　薬物治療学分野）

Abstract；
We have reported an impact of the cytochrome P450 (CYP) 2C19 genotype on the efficacy of clobazam (CLB) therapy, but we have not confirmed whether the genotype affected the adverse effect. CLB-induced weight gain is observed commonly in Japanese, though it is rare in Caucasians. We therefore investigated the association between the CYP2C19 genotype and body mass index (BMI) in 50 and 115 Japanese children under CLB or the other anticonvulsant therapy, respectively. Overweight and obesity were diagnosed according to the age- and sex-specific cut-off value of BMI, ≥25 kg/m2 and ≥30 kg/m2, respectively; and the BMI gap from an age- and sex-adjusted BMI of 25 kg/m2 was calculated. The incidences of overweight and obesity were higher in poor metabolizers (PMs) than in extensive metabolizers (EMs), 66.7% vs. 23.7%, P<0.05; and 41.7% vs. 2.6%; P<0.01; respectively, with an adjusted odds ratio of 6.6 for overweight, P=0.014. The mean maximum BMI gap under CLB therapy was also greater in PMs than EMs, 3.54 kg/m2 vs. -1.92 kg/m2, P<0.01. Under the other anticonvulsants, however, the incidence of overweight or obesity and BMI gap did not differ between the genotypes. In conclusion, the CYP2C19 PM genotype, which is more frequent in Japanese (20%) than in Caucasians (1-8%), was a significant risk factor for CLB-induced weight gain.