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

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 147B; no. 5; pp. 594 - 599
• Main Authors: Gau, Yung-Tian A., Liou, Ying-Jay, Yu, Younger W.-Y., Chen, Tai-Jui, Lin, Ming-Wei, Tsai, Shih-Jen, Hong, Chen-Jee
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 05.07.2008; Wiley-Liss
• Subjects: Adult; Adult and adolescent clinical studies; Antidepressive Agents, Second-Generation - pharmacology; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Case-Control Studies; Depression; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - genetics; Female; Genetic Variation; Humans; major depressive disorder; Male; Medical genetics; Medical sciences; Miscellaneous; Mood disorders; p75 neurotrophin receptor; pharmacogenetics; Polymorphism, Single Nucleotide; polymorphisms; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Receptor, Nerve Growth Factor - genetics; Receptor, Nerve Growth Factor - metabolism; Serotonin Uptake Inhibitors - pharmacology; Mood disorder; Neurotrophin; Pharmacogenetics; Psychotropic; p75 neurotrophin receptor; Genetic variant; Depression; polymorphisms; Association; Gene; major depressive disorder; Genetics; Antidepressant agent; Chinese; Polymorphism; Biological receptor
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30646

The p75 neurotrophin receptor (p75NTR) 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 (p75NTR 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 p75NTR 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 p75NTR TCT carriers had a more unfavorable response to therapy (P = 0.010). Our exploratory study has demonstrated the association between p75NTR and SSRI response for the first time, which may assist in individualized therapy for MDD patients in the future. © 2007 Wiley‐Liss, Inc.