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.
Gau
Yung-Tian A
YT
School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Liou
Ying-Jay
YJ
Yu
Younger W-Y
YW
Chen
Tai-Jui
TJ
Lin
Ming-Wei
MW
Tsai
Shih-Jen
SJ
Hong
Chen-Jee
CJ
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D020800:Receptor, Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D018687:Antidepressive Agents, Second-Generation; D020800:Receptor, Nerve Growth Factor; D017367:Selective Serotonin Reuptake Inhibitors