Association of Two Variable Number of Tandem Repeats in the Monoamine Oxidase A Gene Promoter with Schizophrenia

BACKGROUND: Monoamine oxidase-A (MAO-A) decomposes dopamine and serotonin, and decreased MAO-A expression increases monoamine levels and is related to the pathophysiology of schizophrenia. Previous studies have reported that variable number of tandem repeats (VNTR), namely, upstream (u)VNTR, and some single nucleotide polymorphisms (SNPs) in the MAOA gene are associated with schizophrenia. METHODS: We investigated the two VNTRs and their related SNPs (rs6323 and rs1137070) in the MAOA gene promoter in 859 patients with schizophrenia and 826 healthy controls. Distal (d)VNTR and uVNTR were genotyped with fluorescence-based fragment polymerase chain reaction assays, and rs6323 and rs1137070 with TaqMan SNP genotyping assays. RESULTS: Neither the genotype nor allelic frequency of the VNTRs or SNPs showed significant differences between the schizophrenia and control groups. On the other hand, analysis of the dVNTR-uVNTR-rs6323-rs1137070 haplotype showed significant association for nine repeats (9R)-3R-T-C in female patients (corrected p = 0.0006, odds ratio [confidence interval] = 2.17 [1.446–3.257]). CONCLUSION: Our findings provide novel evidence that MAOA gene polymorphisms are associated with an increased risk of developing schizophrenia in females.