Association study of interaction of tryptophan hydroxylase 2 with serotonin 1A receptor gene polymorphism on major depressive disorder

Objective To explore the interaction between tryptophan hydroxylase 2(TPH2) gene polymorphisms (rs4570625, rs11178997) and serotonin 1A receptor(5-HT1A) gene polymorphisms (rs878567, rs1364043, rs6265) and the association with major depressive disorder (MDD) in a Chinese Han population. Methods The DNA isolated from peripheral blood samples of 288 MDD patients 288 healthy subjects was detected by single base primer extension assay (Snapshot). The generalized multifactor dimensionality reduction (GMDR) method was used to analyze the gene-gene interaction. Results Significant differences were found in the genotype(patients (TT: 27, TA: 152, AA: 109), controls (TT: 82, TA: 105, AA: 101), P<0.01) and allele(patients (T: 206, A: 370), controls (T: 269, A: 307), P<0.01) frequencies of rs11178997 within TPH2 between MDD patients and controls. Statistically, a greater risk of developing MDD was found in individuals with an rs11178997 A-allele(OR=1.574, 95%CI=1.243-1.993). The interaction between TPH2 (rs4570625, rs11178997) and 5-HT1A (rs878567, rs1364043, rs6265) was considered as the best multi-locus model, and this showed a testing accuracy of 57.67% and a CV consistency of 10/10. And this interaction had a significant effect on the risk of MDD (P=0.0107). Conclusion There may be an association between the interaction of TPH2 and 5-HT1A polymorphisms and MDD. Key words: Major depressive disorder; Tryptophan hydroxylase 2; Serotonin 1A receptor; Gene-gene interaction