One hundred and five patients with major depression and 74 unrelated matched controls were analyzed for a silent 1287G/A polymorphism (NET-8) in exon 9 of the NET gene.
Our results suggest that CYP2D6 ultra-rapid metabolizer status contributes to venlafaxine-XR treatment remission in MDD patients; in particular, there is a PK-PD interaction with treatment remission associated with CYP2D6 URM phenotype and SLC6A4 5-HTTLPR L/L or SLC6A2 G1287A G/A genotype, respectively.
In the haplotype analysis, TAA (rs2242446-rs28386840-rs5569, from left to right) was associated with suicide attempts in MDD, although the significance (p=0.043) disappeared after Bonferroni correction.
In a case control association study we investigated the newly identified T-182C polymorphism and an already known G1287A polymorphism in exon 9 of the NET gene in a sample of 193 patients with major depression and 136 healthy, non-related controls.
We analyzed the NET promoter T-182C polymorphism and another silent polymorphism G1287A in exon 9 of the NET gene with a polymerase chain reaction (PCR)-based method in 216 patients with major depression and 210 unrelated, age-and sex-matched healthy control subjects.
In self-identified white patients with major depressive disorder (N=126) treated with open-label duloxetine (60-120 mg/d), a significant association of (P=0.020) of a composite risk score (based on SLC6A2 rs5569 [G1287A] AA, HTR1A rs6295 [C(-1019)G] GG, and COMT rs174697 AA/AG) with 17-item Hamilton Depression Rating Scale total score change from baseline to 12 weeks was observed.
The present study suggests that the combined effect of rs2242446 and rs5569 in the NET gene could modify the response to the negative life events in triggering MD.