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Methionine homozygosity at codon 129 in the prion protein is associated with white matter reduction and enlargement of CSF compartments
Twin studies point towards a substantial heritability of brain structure. The genetic pathways which influence brain morphogenesis as well as its interindividual variance remain largely unknown. Schizophrenia is a psychiatric disorder which shows a significant genetic component and also is associated with slight changes in brain morphology. The prion protein (PRNP) aids cellular resistance to oxidative stress and neurodegeneration and is involved in neurodevelopment.
This study examines the influence of a polymorphism in the PRNP gene on brain morphology in 47 healthy and 43 male schizophrenic patients. All subjects underwent identical MRI scanning sessions and genotyping for a polymorphism in PRNP (Met129Val).
The allelic distribution did not differ and we also did not find any differences of gene effects on brain morphology related to diagnosis. However, we found influences of the prion genotypes in our whole sample: methionine-homozygotes revealed general reduced white matter volumes and enlargements of CSF.
These results suggest a role of PRNP in brain morphogenesis, mainly white matter, and confirm the lack of involvement in schizophrenia pathogenesis.