The Gender-Specific Interaction of and Polymorphisms on Major Depressive Disorder Susceptibility in a Chinese Han Population: A Case-Control Study.

Based on the "oxidative stress hypothesis" of major depressive disorder (MDD), cells regulate their structure through the Wnt pathway. Little is known regarding the interactions of dishevelled 3 () and glycogen synthase kinase 3 beta () polymorphisms with MDD. The aim of the current study was to verify the relationship between and genetic variants in a Chinese Han population and further to evaluate whether these interactions exhibit gender-specificity. A total of 1136 participants, consisting of 541 MDD patients and 595 healthy subjects, were recruited. Five single-nucleotide polymorphisms (SNPs) of / were selected to assess their interaction by use of a generalized multifactor dimensionality reduction method. The genotype and haplotype frequencies of / polymorphisms were significantly different between patients and controls for rs1709642 ( < 0.01) and rs334558, rs6438552, and rs2199503 ( < 0.01). In addition, our results also showed that there were significant interaction effects between and polymorphisms and the risk of developing MDD, particularly in women. The interaction between (rs1709642) and (rs334558, rs6438552) showed a cross-validation (CV) consistency of 10/10, a value of 0.001, and a testing accuracy of 59.22%, which was considered as the best generalized multifactor dimensionality reduction (GMDR) model. This study reveals the interaction between and polymorphisms on MDD susceptibility in a female Chinese Han population. The effect of gender should be taken into account in future studies that seek to explore the genetic predisposition to MDD relative to the and genes.