Analysis of the association of and its target gene polymorphisms with major depressive disorder and antidepressant response.

BACKGROUND

Increasing evidence has indicated that dysfunction of miR-124 and target gene regulator of G protein signaling 4 () may be involved in the etiology and treatment of major depressive disorder (MDD). However, the molecular mechanisms are not fully understood. This study aimed to investigate whether common genetic variations in these two genes are associated with MDD and therapeutic response to antidepressants in the Chinese population.

METHODS

Three polymorphisms including rs531564 (a functional single-nucleotide polymorphism [SNP] in ), rs10759 (a microRNA-binding site SNP in ), and rs951436 (a promoter SNP in ) were genotyped in 225 Chinese MDD patients and 436 controls. Among the MDD patients, 147 accepted antidepressant treatment for 8 weeks with therapeutic evaluation at baseline, week 2, week 4, week 6, and week 8 using the 17-item Hamilton Rating Scale for Depression. Multifactor dimensionality reduction (MDR) was used to identify gene-gene interactions.

RESULTS

No significant association with MDD was discovered in single-SNP analyses. However, by MDR analysis, the three-locus model of gene-gene interaction was the best for predicting MDD risk. In pharmacogenetic study, a significant association was found in genotypic frequencies of rs951436 between the remitter and non-remitter groups (=0.026, correction =0.078). For further analysis, the rs951436 heterozygote carriers had threefold probabilities of achieving clinical complete remission (odds ratio =3.00, 95% confidence interval =1.33-6.76, =0.007, correction =0.021) as compared with rs951436 homozygotes (AA+CC) after 8 weeks of treatment.

CONCLUSION

An interaction effect of and polymorphisms may play a more important role than individual factors for MDD development. Moreover, gene polymorphisms may be associated with antidepressant response among the Han population.