A variant in the 3ʹ-untranslated region of the MC2R gene decreases the risk of schizophrenia in a female Han Chinese population

OBJECTIVE: Schizophrenia is a complex mental disorder with high heritability. The hypothalamic–pituitary–adrenal (HPA) axis, which is the stress system of the neuroendocrine system, is considered to impact psychotic disorders. We hypothesized that polymorphisms of HPA axis genes might be involved in the development of schizophrenia. METHODS: A case–control study comprising 234 patients with schizophrenia and 399 matched healthy controls was conducted to investigate the association between the human melanocortin 2 receptor (MC2R) gene and schizophrenia risk. Seven tag single nucleotide polymorphisms (SNPs) (rs16941303, rs16941314, rs2186944, rs28926188, rs7230126, rs948322, and rs948331) of MC2R were genotyped by direct sequencing. RESULTS: No significant associations were observed between any of the alleles, genotypes, or haplotypes examined within the MC2R gene and the risk of schizophrenia in the total group or in subgroups stratified by smoking or alcoholism. However, a subgroup analysis stratified by sex revealed that under the additive model, the C allele of the MC2R rs948331 SNP significantly decreased the risk of schizophrenia in females (odds ratio=0.18). CONCLUSION: The C allele of the MC2R rs948331 locus may be a protective factor, reducing the risk of schizophrenia in the female Han Chinese population.