Association study of polymorphisms in CYP2D6,CYP2C9and CYP2C19 genes and fluoxetine response in patients withMajor depressive disorder

• Main Authors: Hsiang-lan Chen, 陳香蘭
• Other Authors: Der-An Tsao
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/89790059431968089891

碩士 === 輔英科技大學 === 醫事技術系碩士班 === 98 === Fluoxetine is a widely used antidepressant. CYP2D6, CYP2C9 and CYP2C19, three cytochrome P450 genes, are involved in the metabolism of fluoxetine and could influence clinical response. The aim of this study was to investigate the role of polymorphisms in the cytochrome P450 CYP2D6, CYP2C9 and CYP2C19 genes for fluoxetine response.There are 120 normal control and one hundred ten hospitalized patients with major depressive disorder received 20 mg/day of fluoxetine for six weeks.Symptom severity was assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17) at weeks 0, 1, 2, 3, 4 and 6. Response was defined as a reduction of 50% or more of the HAMD-17 total score following 6 weeks of treatment. In order to determine whether genetic polymorphisms at CYP2D6 , CYP2C9 and CYP2C19 is associated with major depression, PCR-RFLP and PCR product sequencing experiments were performed to identify genetic polymorphisms in CYP2D6 rs16947 and CYP2C19 rs4244285、rs4986893 of major depression patients and unrelated of non-major depression subjects blood.A total of 65 (59.1%) of the 110 completers were classified as responders after six weeks of treatment. There are no significant differences between the responders and nonresponder with respect to sex (p = 0.10), age (p = 0.48), age onset of major depressive episode (p = 0.19), numbers of previous episode (p =0.12) and baseline HAMD-17 scores (p = 0.31). No associations with CYP2D6*2 (2850C>T), CYP2C19*2 (681G>A), or CYP2C19*3 (636G>A) genes polymorphisms and the response to fluoxetine were found (p = 0.695, p = 0.948, and p =0.894 respectively) . These results suggest that the polymorphisms of CYP2D6*2, CYP2C19*2 and CYP2C19*3 genes should be unlikely to play a major role in the fluoxetine response. Nevertheless, methodological and sample size limitations of this study do not allow definitive conclusions.