Influence of genetic polymorphisms in homocysteine and lipid metabolism systems on antidepressant drug response.

Background: Variation 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.

Methods: A 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.

Results: In 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.

Conclusions: Genetic 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.