Evidence for association between genetic variants of p75 neurotrophin receptor (p75NTR) gene and antidepressant treatment response in Chinese major depressive disorder.

The p75 neurotrophin receptor (p75(NTR)) is an essential component of neurotrophin system, and has been implicated in the pathogenesis of major depressive disorder (MDD) and in the mechanism of antidepressant action. This study aimed to delineate the association between phenotype (MDD susceptibility and antidepressant response) and genotype (p75(NTR) common genetic variants) in a Chinese population. A total of 228 MDD patients and 402 unrelated controls were recruited. Subjects took selective serotonin reuptake inhibitors (SSRIs) and responders were defined as those with at least a 50% decrease in score of the Hamilton Rating Scale for Depression (HAM-D) from baseline. Five p75(NTR) polymorphisms were genotyped and their association with MDD or treatment response was assessed by haplotype and single marker analysis. No significant association with MDD was discovered in single locus or haplotype analyses. With regard to the therapeutic outcome, however, one missense polymorphism (S250L) showed association in both genotype distribution (P = 0.039) and allele frequency (P = 0.012). Haplotype analysis also revealed that p75(NTR) TCT carriers had a more unfavorable response to therapy (P = 0.010). Our exploratory study has demonstrated the association between p75(NTR) and SSRI response for the first time, which may assist in individualized therapy for MDD patients in the future. Copyright 2007 Wiley-Liss, Inc.