| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
Objective : We investigated the relevance of phenotypes and genotypes of drug metabolizing enzymes to the individual susceptibility to adverse drug reactions (ADRs) and/or metabolic syndrome (MS).
Methods : Japanese participants in a health screening program were asked to describe any past history of ADRs. Any subjects reporting ADRs were then individually interviewed. H1-antihistamine-induced excessive daytime sleepiness was assessed by the Epworth sleepiness scale (ESS), and an ESS score 【greater than or equal】 12 was diagnosed to be hypersomnia. CYP2D6 were genotyped by a panel of polymerase chain reaction techniques. In addition, the relevance of serum xanthine oxidase (XO) activity to the MS susceptibility was investigated in other 126 volunteers. The study protocol was approved by Institutional Review Boards.
Results : Out of 2,074 participants, 246 cases (11.9%) experienced ADRs. Among them, 10 cases and 59cases had severe ADRs and recurrence(s), respectively. Approximately 75% of ADRs could have been prevented or mitigated. The frequency of the occurrence of ADRs was two times higher in females than in males (p<0.05). As for H1-antihistamine induced ADRs, 100 cases were eligible for analysis. CYP2D6^*10 allele and genotypes were more frequently found in the cases than in controls (P < 0.05), but no difference was observed in the null alleles and genotypes. The occurrence of hypersomnia increased as the number of CYP2D6 mutant alleles increased (P=0.045). The serum XO activity increased as the score of diagnostic criteria for MS and the serum triglyceride concentration (P<0.0001 and rs=0.8585, P<0.0001, respectively).
Conclusion : The results indicated the high prevalence of ADRs, especially in females and suggested the presence of the CYP2D6^*10 allele might be a risk factor for developing H1-antihistamine-induced hypersomnia in Japanese, and serum XO activity might be a biomarker of MS.
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