Female-specific associations of glyoxalase 1 polymorphisms with schizophrenia in a Han Chinese case–control study

BACKGROUND: Emerging evidence suggests that glyoxalase 1 (Glo-1) may contribute to sex-specific phenotypes in schizophrenia. This study aims to investigate the sex-specific effects of Glo-1 polymorphisms on schizophrenia susceptibility. METHODS: Four Glo-1 genetic polymorphisms were genotyped using SNaPshot technology in a sample of 1214 schizophrenic patients and 1138 age- and sex-matched healthy controls. RESULTS: Significant associations were found between schizophrenia and control groups in both genotypic [P = 0.044, false discovery rate (FDR) correction] and allelic (P = 0.036, FDR correction) distributions of the rs1781735 polymorphism, whereas no significant difference for rs9470916, rs4746, or rs1130534 (P > 0.05). Haplotype analysis for the rs9470916-rs1130534-rs4746-rs1781735 haplotype revealed significant associations with schizophrenia, particularly for the C-T-A-G haplotype, which was less frequent in schizophrenic patients than controls [odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.98, P = 0.024]. In sex-stratified analyses, significant associations in females were observed for rs1781735 (P = 0.020 for genotype, P = 0.004 for allele, FDR correction), rs1130534 (P = 0.037 for genotype, P = 0.011 for allele, FDR correction), and rs9470916 (P = 0.020 for genotype, P = 0.004 for allele, FDR correction). Furthermore, haplotype analysis identified female-specific associations for the C-T-A-G (OR = 0.73, 95% CI = 0.59-0.91, P = 0.005) and A-A-A-T (OR = 1.38, 95% CI = 1.08-1.75, P = 0.009) haplotypes, whereas no associations were detected in the male subgroup. CONCLUSIONS: Single-nucleotide polymorphisms in Glo-1 exhibited a female-specific association with schizophrenia in a Han Chinese cohort, suggesting a potential sex-specific role of Glo-1 in schizophrenia susceptibility.