Glial cell line-derived neurotrophic factor (GDNF) gene and schizophrenia:polymorphism screening and association analysis

The glial cell line-derived neurotrophic factor (GDNF) is an important neur otrophic and potential differentiation factor for dopaminergic systems. Bot h the dopamine theory and the neurodevelopmental hypothesis of schizophreni a suggest that alterations of GDNF functions could be involved in the patho genesis of schizophrenia. Using polymerase chain reaction and single strand conformational polymorphism analysis, we searched for polymorphisms in the GDNF gene in 50 patients with schizophrenia. No evidence was obtained, how ever, for the presence of polymorphisms in the DNA sequence encoding GDNF m ature peptide in our patients. We then examined a trinucleotide repeat (AGG )(n) polymorphism in the 3'-UTR of the GDNF gene for allelic association in a Japanese sample of 99 schizophrenic patients and 98 control subjects. Th ere was no significant difference in the overall distribution of the allele between the two groups. When each allele was examined separately, the alle le (AGG)(10) was more common in schizophrenic patients than in control subj ects, but this finding was not significant when multiple testing was taken into account in the analysis. Overall, we obtained no solid evidence for th e involvement of the GDNF gene in the pathogenesis of schizophrenia, althou gh further studies in larger numbers of subjects will be required to conclu de whether the trinucleotide repeat polymorphism is associated with the dev elopment of schizophrenia. (C) 2001 Elsevier Science Ireland Ltd. All right s reserved.