Support for association between the Ser205Leu polymorphism of p75NTR and major depressive disorder

Abstract

Altered neurotrophin functions have been implicated in major depressive disorder (MDD). Previously, we reported an association between MDD and a missense polymorphism (Ser205Leu: rs2072446) of the gene encoding the p75 neurotrophin receptor (p75 NTR ). However, contradictive negative results have also been reported. This study tried to replicate the association in an independent sample. Subjects were 668 patients with MDD and 1130 healthy controls. The proportion of individuals carrying the Leu205 allele was significantly decreased in the patients than in the controls (v 2 ¼5.3, d.f.¼1, P¼0.021, odds ratio (OR) 0.74, 95% confidential interval (CI) 0.58-0.96). When allele frequencies were compared, the Leu205 allele was significantly reduced in the patients than in the controls (v 2 ¼4.4, d.f.¼1, P¼0.037, OR 0.78, 95% CI 0.61-0.99). When men and women were examined separately, there was a significant difference in genotype and allele distributions in women (genotype: v 2 ¼8.3, d.f.¼1, P¼0.0039, OR 0.60, 95% CI 0.43-0.85; allele: v 2 ¼7.3, d.f.¼1, P¼0.0069, OR 0.64, 95% CI 0.47-0.89), but not in men. The present study provided support for the previously reported association between the Ser205Leu polymorphism of the p75 NTR gene and MDD, indicating that the Leu205 allele has a protective effect against the development of MDD, particularly in women.

Single-Nucleotide Polymorphisms in TrkB and Risk for Depression

“…This SNP has been suggested to exert a protective effect against the development of MDD in a cohort of female Japanese subjects. 27 Our data suggest no association between this SNP and depressive symptoms in either HIV positive or negative women. However, the genetic background of our samples differs from those used in previous studies, as does our definition of “depressed”, which was not based on a clinical diagnosis of MDD.…”

NGF (−198C > T, Ala35Val) and p75NTR (Ser205Leu) gene mutations are associated with liver function in different histopathological profiles of the patients with chronic viral hepatitis in the Brazilian Amazon

“…In contrast, the SerSer variant of the Ser205Leu polymorphism, a variant with a conserved receptor structure (Fujii et al, 2011;Gau et al, 2008), showed low viral loads and elevated liver enzyme activity levels in moderate/severe inflammation, suggesting that the wild-type p75 NTR pathway favors liver injury in individuals with advanced stages of inflammatory activity, as shown in different cell lines in which the p75 NTR pathway stimulates the production of proinflammatory cytokines that contribute to chronic tissue injury (Minnone et al, 2017;Elshaer and El-Remessy, 2017).…”

“…The change in the peptide is related to structural changes, cellular localization and receptor signaling (Cohen-Cory et al, 1991;Drysdale et al, 2000). This SNP is associated with depressive disorder in Japanese women (Fujii et al, 2011) and Alzheimer's disease (Lester et al, 2012), and the Leu variant has a protective role against the development of these disorders, although heterozygous patients have a weaker response to antidepressants than do patients homozygous for Ser +/+ (Gau et al, 2008). The selection of SNPs representative of haplotypes (tag SNPs) is being used as a way of representing the biological significance of the genetic variations of p75 NTR (Wang et al, 2014).…”

Association between genetic variants related to glutamatergic, dopaminergic and neurodevelopment pathways and white matter microstructure in child and adolescent patients with obsessive–compulsive disorder

“…The two polymorphisms located in NGFR, rs734194 and rs2072446, have been previously reported to be involved in major depressive disorder and Alzheimer's disease (Cheng et al, 2012;Cozza et al,2008;Fujii et al, 2011). Neurotrophic factors (NF) such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are involved in axon growth, dendrite pruning and the expression of proteins crucial for normal neuronal function, such as neurotransmitters and ions channels (Huang and Reichardt, 2001).…”