Association between Unc-51-like autophagy activating kinase 2 gene polymorphisms and schizophrenia in the Korean population

Abstract

Accumulating evidence indicates that the autophagy process is involved in the pathogenesis of schizophrenia. Autophagy plays a fundamental role in neuronal survival and function, and autophagy-related genes have been suggested to be associated with the pathogenesis of schizophrenia. The Unc-51-like autophagy activating kinase 2 (ULK2) gene has been implicated in autophagy regulation; therefore, we hypothesized that ULK2 polymorphisms may be associated with schizophrenia susceptibility.This study explored the association between polymorphisms of ULK2 and schizophrenia.Two single nucleotide polymorphisms (SNPs) (rs55730189 and rs150122) of ULK2 were genotyped in 279 patients with schizophrenia and 403 healthy individuals using Fluidigm SNPtype assays. We analyzed the genotype distribution of 2 SNPs and haplotypes between patients with schizophrenia and control subjects.The T allele frequency of rs55730189 showed a significant association between patients with schizophrenia and control subjects (P = .003). Genotype frequencies of rs55710189 were found to be significantly different between patients with schizophrenia and control subjects (odds ratio = 6.89, 95% confidence interval = 1.91-24.90, P < .001 in the dominant model [C/T + T/T vs C/C], OR = 6.50, 95% confidence interval = 1.83-23.01, P < .001 in the log-additive model (C/T vs T/T vs C/C)]. In haplotype analysis, the TT haplotype for these 2 SNPs was significantly associated with schizophrenia (P < .001, χ2 = 12.231).Our findings suggest that specific ULK2 polymorphisms may be associated with susceptibility to schizophrenia in the Korean population.