Association of CYP1A2 and CYP2D6 gene polymorphism with therapeutic efficacy of duloxetine on depression in southern region of Fujian / 中华行为医学与脑科学杂志

ABSTRACT

Objective To explore the influence of CYP1A2 and CYP2D6 gene polymorphism on blood concentration,therapeutic efficacy and adverse effects of anti-depression drug duloxetine on depression patients in southern region of Fujian.Methods 82 patients with depression were selected from southern region of FuJian, China,and all participates received duloxetine for two weeks.Blood concentrations of duloxetine were detected by HPLC-MS,and CYP1A2 and CYP2D6 genotypes were determined by sequencing with the amplified PCR products from peripheral blood DNA.The therapeutic efficacy and adverse effects of duloxetine were evaluated by Hamilton depression scale (HAMD) and treatment emergent symptom scale (TESS) respectively.Results Subjects were divided into GG,GA and AA three groups based on CYP1A2 * 1C genotyping.There was no significant difference in blood concentrations of duloxetine, dose-corrected blood concentrations, the reduction rate of HAMD and the reduction rate of TESS among the three groups.Results were the same with CYP1A2 * 1F,which were divided into CC, CA and AA three groups.Subjects was divided into CC, CT,TT three groups based on CYP2D6 * 10 locus genotyping.Blood concentrations of duloxetine were (13.89±3.22) ng · ml-1 , (16.08±4.24) ng · ml-1 , (17.25±4.62) ng · ml-1 respectively and there was significant difference(F=3.21, P＜0.05).CC group was significantly lower than TT group(P＜0.05) , and CT group was lower than TT group but without significant difference (P＞0.05).Dose-corrected blood concentrations were (304.84± 103.76), (368.13± 143.49), (444.50± 195.58) respectively and there was significant difference(F=4.19, P＜0.05), and CC group was significantly lower than TT group (P＜0.05).The reduction rate of HAMD were 0.42±0.11,0.46±0.11,0.52±0.09 respectively and there was significant difference (F =6.29, P＜0.05), and CC and CT group was significantly lower than TT group(P＜0.05).The reduction rate of TESS were 1.14±0.66,1.48±0.69, 1.69±0.69 respectively and there was significant difference(F=3.38, P＜0.05).CC group was significantly lower than TT group(P＜0.05).Conclusion Among the 3 loci studied,only CYP2D6 * 10 locus within CYP2D6 gene can affect blood concentration,efficacy and adverse effects of duloxetine,which indicate that CYP2D6 gene polymorphism may contribute to therapeutic efficacy of duloxetine on depression in southern region of Fujian.