|Title:||CYP1A2 genetic polymorphisms are associated with treatment response to the antidepressant paroxetine||Authors:||Lin K.-M.
|Issue Date:||2010||Journal Volume:||11||Journal Issue:||11||Start page/Pages:||1535-1543||Source:||Pharmacogenomics||Abstract:||
Aim: Paroxetine is a drug of choice in the treatment of major depressive disorder (MDD). Its metabolism has recently been reported to be mediated through the CYP enzymes 1A2 and 2D6. In our current study, we tested whether genetic polymorphisms in CYP1A2 are associated with the treatment efficacy and side effects of paroxetine. Materials & methods: A total of 241 MDD patients who had taken paroxetine continually for 8 weeks were recruited, and their steady state paroxetine concentrations were measured at weeks 2, 4 and 8. The genotypes of these patients were then assessed for the presence of nine SNPs, which were selected from either the HapMap Chinese ethnic group, the literature report or through their functional role in the CYP1A2 gene. Results: The allele types for SNPs rs4646425 (permutation p = 0.03), rs2472304 (permutation p = 0.01) and rs2470890 (permutation p = 0.004) demonstrated significant associations with paroxetine treatment remission at week 8. Response rates in the Hamilton Rating Scale for Depression (HAM-D) and for The Hamilton Rating Scale for Anxiety (HAM-A) were significantly associated with the SNPs rs4646425 (p = 0.0126 and 0.0088 for HAM-D and HAM-A, respectively) and rs4646427 (p = 0.0067 and 0.0196 for HAM-D and HAM-A, respectively). The inducible SNP rs762551 had a significant association with paroxetine dose at week 4 (permutation p = 0.012). We did not find an association between these SNPs and the side effects or serum concentrations of paroxetine. Conclusion: Genetic variants in the CYP1A2 region may be indicators of treatment response in MDD patients to paroxetine. ? 2010 Future Medicine Ltd.
|ISSN:||1462-2416||DOI:||10.2217/pgs.10.128||SDG/Keyword:||cytochrome P450 1A2; imipramine; lorazepam; paroxetine; zolpidem; adult; anxiety disorder; article; blood sampling; Chinese; controlled study; diagnostic and statistical manual of mental disorders; drug blood level; drug efficacy; drug response; ethnicity; evening dosage; female; gene frequency; gene linkage disequilibrium; gene locus; genetic polymorphism; genotype; Hamilton Anxiety Scale; Hamilton scale; haplotype; haplotype map; human; major clinical study; major depression; male; onset age; protein function; single nucleotide polymorphism; steady state; Adult; Antidepressive Agents, Second-Generation; Cohort Studies; Cytochrome P-450 CYP1A2; Depressive Disorder, Major; Female; Humans; Male; Paroxetine; Polymorphism, Single Nucleotide; Treatment Outcome
|Appears in Collections:||生物化學暨分子生物學科研究所|
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