Gender-specific role of the protein tyrosine phosphatase receptor type R gene in major depressive disorder.

Major depressive disorder (MDD) is a common, chronic, and recurrent mental disease affecting millions of individuals worldwide. The precise mechanism by which the illness is developed remains unknown, but it has been accepted that a genetic component is very likely to be involved. Studies of the pathogenesis of MDD have implicated a reduced activity of the extracellular regulated kinase (ERK) signaling system. Protein tyrosine phosphatase, receptor type R (PTPRR) is a key negative regulator of the ERK signaling pathway and its expression is regulated by androgen. Therefore, it is worth testing whether the PTPRR gene could confer a risk of MDD. We genotyped 16 SNPs in the PTPRR locus with the MALDI-TOF-MS-based genotyping protocol in 517 patients with MDD and 455 controls among a Chinese Han population. The UNPHASED program was applied to analyze the genotyping data. Of the 16 SNPs selected, rs1513105 was the only one showing allelic association (χ2=9.019, p=0.0027) and genotypic association (χ2=8.813, df=2, p=0.012), of which the rs1513105(C) allele was associated with an increased risk of MDD (OR=1.331, 95% CI 1.104-1.604), but the rs1513105 association resulted mainly from female subjects (χ2=12.35, p=0.00044 for allelic association; χ2=11.26, df=2, p=0.0036 for genotypic association). Replication and functional study may be required to draw a firm conclusion. Our results suggest that the PTPRR gene may play a role in conferring risk of MDD in the female subjects.