The Association Study Of CLOCK Gene Polymorphisms With Antidepressant Effect In Chinese With MDD

Objective:Major Depressive Disorder?MDD?is a common psychiatric disorder,with complicated pathogenesis and genetic predisposition.Previous studies manifested,the biological rhythms play an important part in the onset and clinical features of MDD.And as we all known,CLOCK is one of the vital genes that regulate biological circadian rhythms.At present,studies on the correlation between CLOCK gene polymorphisms and MDD at home and abroad mostly focus on etiology.Moreover,it has not been reported that CLOCK gene polymorphisms are significantly associated with antidepressant efficacy in Chinese population.The purpose of this study was to analyze the relationship between CLOCK gene polymorphism and antidepressant efficacy,depressive symptoms and side effects of SSRIs in Chinese Han MDD patients.Methods:600 subjects with MDD,who met the DSM-?diagnostic criteria,were recruited.All subjects were treated with single SSRIs,Including:escitalopram,citalopram etc.A total of 331 subjects completed six weeks of treatment.17item-Hamilton depression scale(HAMD₁₇)and adverse reaction scale?TESS/UKU?were used to assess the efficacy of antidepressants and adverse effects every two weeks.The scores of 7 syndrome factors at the baseline of HAMD₁₇ were analyzed to reflect the clinical characteristics of all subjects.PCR and DNA sequencing analysis were used to genotype 4 polymorphism loci of CLOCK gene.Genotypic frequencies distribution were compared among different groups by Pearson?2.The scores of HAMD₁₇ in different genotypes were compared using independent-samples T test or one-way ANOVA.SPSS19.0 software was used for statistical analysis.Results:1.Hardy-Weinberg genetic balance?HWE?testFour SNPS of CLOCK gene in this study,namely rs11932595,rs12504300,rs3805148and rs534654,were consistent with the Hardy-Weinberg genetic balance?P>0.05?after goodness of fit test analysis,indicating that the sample population in this study was representative of the population.2.General demography data analysisThe differences of gender,age,marital status,family history,HAMD₁₇7 baseline score and HAMD₁₇ 6-week score in the different groups were analyzed.There was a significant difference in marital status?P=0.000?between the effective group and the ineffective group.There was a significant difference in HAMD₁₇ 6-week score between the effective group and the ineffective group?P=0.000?,and there was also a significant difference between the remission group and the non-remission group?P=0.000?.There was no significant difference in other general data between the two groups?P>0.05?.3.SNPs and antidepressant efficacyThe study found that the difference of rs11932595 genotype distribution between the effective group and the ineffective group was statistically significant?P=0.035?,that is,the individual effective rate?AA genotype?without G allele was higher than that with G allele?GG+GA genotype???²=4.445,OR=2.31?.But the above result cannot pass the FDR?False Discovery Rate?adjustment?P=0.070?.There was no significant difference in the distribution of SNPs genotypes between the remission group and the non-remission group?P>0.05?.4.SNPs and depressive symptomsSignificant difference was observed that subjects with rs534654 GG genotype had lower scores in HAMD₁₇ syndrome factor 7?weight loss?than those with AG genotype.?P=0.010?.5.SNPs and adverse effectCarriers of the GG genotype in rs12504300 were 5.56 times more likely to suffer from nausea&vomiting than those with CC+GC genotypes?P=0.012,?²=6.339,OR=5.56?;and Carriers of the AA genotype in rs3805148 were 4.26 times more likely to suffer from constipation and 4.93 times more likely to suffer from nausea&vomiting than those with CC+CA genotypes?P=0.016,?²=5.784,OR=4.26;P=0.021,?²=5.304,OR=4.93?.Conclusion:1.The SNP rs11932595 of CLOCK gene may be associated with the efficacy of SSRIs in Chinese Han MDD patients.2.The SNP rs534654 of CLOCK gene may be related to the weight loss feature in MDD patients.3.The SNPs rs12504300 and rs3805148 of CLOCK gene may be associated with the adverse effect during the treatment of SSRIs.