Genes Analysed for Association with Autism and DBH Level

Background: Previous studies have shown decreased DBH activity in individuals with autism compared with age-matched controls. This finding was replicated in the Irish Autism sample. Markers in the DBH gene, including rs1611115, were found not to be responsible for the decrease in activity.

Objectives: This study aimed to identify alternative genes within the Dopamine (DA) pathway and those known to interact with DBH, which may exert an influence over DBH expression or activity.

Methods: Tagging SNPs in transcription factors, DA pathway enzymes and two copper transporters known to interact with DBH/ DA pathway were genotyped. Markers were analysed for association with autism using PLINK. QTL analysis was also undertaken to identify markers associated with DBH activity in the proband and unaffected parent samples.

Results: Markers in AKR1A1 (rs2088102, p=0.033), MAO A/B (rs6651806 p=0.046; rs5905512 p=0.047) and ATP7A (rs1062472 p=0.0086, rs17218310 p=0.035, rs17139614 p=0.035) showed association with autism at the single marker level. Haplotypes in AKR1A1, COMT, ATP7A and ATP7B also showed association with autism. In the proband sample, association with DBH activity was seen in COMT (rs740601 p=0.034, rs4680 p=0.012, rs174696 p=0.014), ATP7A (rs17303393 p=0.034) and MAO A/B (rs12843533 p=0.046). In the parent sample, association was seen with markers in ATP7B (rs9526810 p=0.035, rs3825526 p=0.04, rs9568682 p=0.034).

Conclusions: These results further support the role of DA system in autism. Moreover, differences in the regulation of DBH activity and possibly the regulation of the DA pathway as a whole between the affected proband sample and the unaffected parent sample were noted.