Correlation Between Polymorphism Of CYP1A2Gene And Antidepressant Clinical Efficacy Of Duloxetine

Objective1. To investigate the distribution of C734A and G-2964A polymorphism ofcytochrome P4501A2gene of the Han depressed patients in Henan Province.2. To investigate the relationship between C734A and G-2964Apolymorphism of cytochrome P4501A2gene and clinical effects and adversereaction of duloxetine.Methods1. Subjects223patients with depression were recruited,all of whom wereChinese Han nationality. All of them meeted the criteria of depressive episode ofCCMD-3and were18~60years old.2. Genotyping polymerase chain reaction-restriction fragmentlengthpolymorphism was employed to identify single nucleotide polymorphism atposition C734A and G-2964A of CYP1A2gene. Then all of the subjects weredivided into three phenotypes.3. Evaluation of clinical efficacy all subjects were treated with duloxetine（60mg/d）for six weeks. The clinical effect of duloxetine was evaluated withHamilton rating scale for depression(HAMD),and adverse reaction of duloxetinewas evaluated with Treatment Emergent Symptoms Scale（TESS）.4. Statistical analysis Hardy-Winberg equilibrium was employed toexamine group representive of sample.The correlation between genotype andclinical effect was analysed by Repeated Measures Analysis ofVariance.Chi-square test was used to identify the correlation between genotypeand adverse reaction. Results1. Distribution of gene polymorphism of CYP1A2/C734A and CYP1A2/G-2964A of Han population in Henan areaIn223patients, the frequency of C/C、C/A and A/A at locus734wasrespectively13.90％、45.74％and40.36％;that of G/G、G/A and A/A at locus-2964was respectively54.71％、36.32％and8.97％.2. Comparison of clinical effect between different genotypesThere were220Patients who completed a full antidepressive treatment.2.1Comparison of the decreasing ratio of HAMD score between differentgenotypes of C734A:at the end of6weeks, general comparing of three genotypegroups,the difference was significan（tp<0.01）; the difference between C/C groupand C/A group was not significant （P>0.05）,however, the difference betweenC/C group and A/A group was significant （p<0.01）, the difference between C/Agroup and A/A group was significant （P<0.01）.2.2Comparison of the decreasing ratio of HAMD score between differentgenotypes of G-2964A: at the end of6weeks, general comparing of threegenotype groups,the difference was significant（p<0.01）; the difference betweenG/A group and A/A group was not significant（P>0.05）,however, the differencebetween G/G group and G/A group was significant （p<0.01）, the differencebetween G/G group and A/A group was significant （p<0.01）.2.3Comparison of the decreasing ratio of HAMD score between differentphenotypes: at the end of6weeks,general comparing of three phenotypegroups,the difference was significant（p<0.01）,and all the differences weresignificant（p<0.01）comparing Pairwise between three phenotype groups.3. Comparison of adverse reaction between different genotypes3cases of223subjects which had droped out in the early stage of treatmentdue to serious adverse reaction were all enrolled in adverse reaction group.3.1Comparison of the occurrence rate of adverse reaction between different genotypes of C734A: general comparing of three genotype groups,the differencewas significant（P<0.01），the difference between C/C group and C/A group wasnot significant （P>0.05）,however, the difference between C/C group and A/Agroup was significan（tp<0.05）, the difference between C/A group and A/A groupwas significant（p<0.01）。3.2Comparison of the occurrence rate of adverse reaction between differentgenotypes of G-2964A:general comparing of three genotype groups,thedifference was significant（P<0.01），the difference between G/A group and A/Agroup was not significant （P>0.05）,however, the differences between G/G groupand the other two groups were all significant （all P<0.01）.3.3Comparison of the occurrence rate of adverse reaction between differentphenotypes:general comparing of three phenotype groups,the difference wassignificant（P<0.05）,and all the differences were significant（all P<0.05）comparing Pairwise between three phenotype groups.Conclusions1. There was no significant difference in distribution of polymorphism ofCYP1A2/C734A between Han depressive patients in Henan area and Han healthypersons in Changsha area, however, there was significant difference in distributionof polymorphism of CYP1A2/G-2964between these two groups.2. The polymorphism of C734A and G-2964A of CYP1A2gene caninfluence the clinical effect and adverse reaction of duloxetine in the treatment fordepression.