DCC gene gene variant linked to schizophrenia
MedWire News: A single nucleotide polymorphism (SNP) in the deleted in colorectal cancer gene (DCC) is associated with schizophrenia susceptibility, results from a Canadian study suggest.
Writing in Schizophrenia Research, Ridha Joober (Douglas Mental Health University Institute, Montreal, Quebec) and team observe that "DCC, a receptor for the guidance cue netrin-1, plays a pivotal role in organizing neuronal circuitry by guiding growing axons and dendrites to their correct targets and by influencing synaptic connectivity."
They explain: "Results from experiments we previously conducted in dcc-heterozygous mice show that DCC plays a critical role in the developmental organization of the mesocorticolimbic dopamine circuitry."
Furthermore, previous research has shown that "reduced expression of DCC during development and/or throughout life confers resilience to the development of schizophrenia-like dopamine and behavioral abnormalities," they add.
To investigate whether DCC is associated with risk for schizophrenia, the team genotyped 556 unrelated patients with the disorder and 208 mentally healthy individuals (controls) for 10 SNPs within this gene.
Genotype frequency distribution analysis revealed that schizophrenia patients were significantly more likely to carry the minor allele of the rs2270954 SNP than controls, at an odds ratio of 3.09. However, this association did not remain significant after correction for multiple comparisons.
Further analysis showed that patients were less likely to be heterozygous at this locus and more likely to be homozygous for the minor allele compared with controls.
The researchers note that "intriguingly, this SNP is located within the 3' untranslated region, an area known to contain a number of regulatory sequences that determine the stability and translation efficacy of mRNA."
There were no significant differences between schizophrenia patients and controls regarding allelic or genotypic distributions of any of the other nine DCC SNPs.
Joober and team conclude: "The findings of the present study provide evidence for an association between schizophrenia and the DCC rs2270954 polymorphism, supporting the idea that DCC may be a novel candidate gene."
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By Mark Cowen