Abstract
BackgroundVariation in genes implicated in homocysteine and lipid metabolism systems may influence antidepressant response for patients with major depressive disorder (MDD). This study aimed to investigate whether association of polymorphisms on the MTHFR, ApoE and ApoA4 genes with the treatment response in MDD subjects.MethodsA total of 281 Han Chinese MDD patients received a single antidepressant drug (SSRI or SNRI) for at least 6 weeks, among whom 275 were followed up for 8 weeks. Their response to 6 weeks’ treatment and remission to 8 weeks’ treatment with antidepressant drugs was determined by changes in the 17-item Hamilton Depression Rating Scale (HARS-17) score. Single SNP and haplotype associations with treatment response were analyzed by UNPHASED 3.0.13. Logistic regression analysis was used to explore the interactions between genotypes and gender or drug type on treatment outcome, only those SNPs that had interactional association with gender or drug type were subjected to further stratified analysis.ResultsIn total group, the haplotype (C-A) in MTHFR (rsl801133 and rs1801131) and the ApoE rs405509 AA genotype were significantly associated with better efficacy of antidepressants; In gender subgroups, only haplotype (C-A) in MTHFR (rsl801133 and rs1801131) was significantly associated with better efficacy of antidepressants in male subgroup; In drug type subgroup, the haplotype (C-A) in MTHFR (rsl801133 and rs1801131) and haplotype (G-C) in ApoE (rs7412 and rs405509) were associated with better efficacy of antidepressants in SNRI treated subgroup; The ApoA4 rs5092 G allele and GG genotype were associated with worse efficacy of antidepressants in SNRI treated subgroup.ConclusionsGenetic polymorphisms in homocysteine and lipid metabolism systems are associated with antidepressant response, particularly for the interactions of the certain genetic with gender or drug type.
Highlights
Variation in genes implicated in homocysteine and lipid metabolism systems may influence antidepressant response for patients with major depressive disorder (MDD)
The present study focused on the Apolipoprotein E (ApoE) gene promoter region and coding region to investigate the relationships between polymorphic loci and antidepressant efficacy
There were no significant differences in age, number of years of education, family history, baseline Hamilton Depression Rating Scale (HDRS)-17 score, or antidepressant agents used between remission and nonremission groups, while the proportion of male patients and number of episodes were significantly higher in the non-remission group than the remission group (t = 2.381, P = 0.018 and t = − 1.983, P = 0.049, respectively), as shown in Tables 1 and 2
Summary
Variation in genes implicated in homocysteine and lipid metabolism systems may influence antidepressant response for patients with major depressive disorder (MDD). One particular focus with respect to the connection between folate and depression has been the enzyme methylenetetrahydrofolate reductase (MTHFR) [16], which synthesizes 5methyltetrahydrofolate, a carbon donor involved in the methylation of homocysteine (Hcy) to methionine. This enzyme is encoded by the MTHFR gene on chromosome 1 locus q36.3 in humans. Various lines of research have suggested MTHFR polymorphisms might enhance the environmental risks (such as low folate intake) for MDD via the interaction between genetic and environmental factors [19]. The first purpose of this study was to investigate how MTHFR polymorphisms affect antidepressant efficacy in Chinese Han MDD population
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