An association study between methamphetamine use disorder with psychosis and polymorphisms in MiRNA

Methamphetamine (MA) is an addictive psychostimulant substance that mainly leads to schizophrenia-like psychotic symptoms. The expression of miRNAs in brain plays an important role in neurological disorders and may affect by genetic variant(s) in the target site (MiRSNPs). In this study, we investigated whether polymorphisms in miRNAs are associated with MA disorder with psychosis.

We carried out a case-control association study in 400 MA users with psychotic characters and 448 controls. Six MiRSNPs with predicted functional relevance miRNAs (miR-181b, miR-181a, miR-15b, miR-let-7e and miRlet-7d) were selected for genotyping. Allele and genotype frequencies were compared between MA users and healthy individuals. The expression of five miRNAs were measured by quantitative real-time RT-PCR in 55 cases and 57 controls. We also explored an expression Quantitative Trait Loci (eQTL) analysis based on the miRNAs expression and SNP genotype.

The SNP rs10760371 within miR-181a was nominally associated with MA disorder (P = 0.046). For rs1099308, rs10760371 and rs10993081 in strong linkage disequilibrium (LD), no significant association had been detected from haplotype analysis. Discrepancy had been found between MA users and healthy individuals (P < 0.01) in terms of the expression of miR-181a, miR-15b, miR-let-7e and miR-let-7d. and no noticeable difference had been found from the eQTL analysis.

Our findings suggest that rs10760371 within miR-181a may relate to the development of MA dependence with psychosis. The miRNAs expression is unlikely to be regulated by the SNPs within it.