Background: MicroRNAs (miRNAs) play a vital role in neurodevelopment and neuronal processes, through regulation of target gene expression. Noncoding variants in the miR-137 gene locus have been reported to increase the risk of schizophrenia. This microRNA has been shown to be involved in different brain processes necessary for neurogenesis, which is an important factor in schizophrenia. Additionally, several of the confirmed or predicted target genes for miR-137 have been associated with schizophrenia risk.
Methods: In the present study, we sequenced the miR-137 gene (including the upstream and downstream region) in 52 Costa Rican trios, consisting of individuals diagnosed with schizophrenia and their parents. A TDT test was performed for the two detected variants: the schizophrenia-associated SNP rs1625579 and a previously reported VNTR located upstream of miR-137.
Results: No association was found between any rs1625579 allele and schizophrenia (X2=1, p=0.32). The minor allele frequency (MAF; corresponding to the C allele) in the Costa Rican sample is 0.08. For the VNTR upstream of miR-137 only the 3 and 4-repeat alleles were found. The frequency of the 4-repeat allele in our sample (MAF) was 0.19. No association (using the TDT test) was detected between any of the alleles and schizophrenia (X2=0.05, p=0.83). However, we found a lower age of onset in the affected individuals with at least one 4-repeat allele, when compared with individuals homozygous for the 3-repeat allele (t=2,3, g.l.=44, p=0,026).
Discussion: Age of onset of schizophrenia has clinical consequences for affected individuals; an early onset of the disorder has been reported to be associated with worse cognitive performance as well as worse functional outcomes. The presence of a higher number of repeats for the VNTR upstream of miR-137 could potentially affect expression of the gene, and in this way have an effect on the age of onset of schizophrenia symptoms. Genotyping of the VNTR in other 100 individuals with schizophrenia is ongoing, in order to confirm the putative role of variants in this locus on age of onset of the disorder.