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Neurosci Lett. 2004 Mar 11;357(3):235-7.

3' UTR (AGG)n repeat of glial cell line-derived neurotrophic factor (GDNF) gene polymorphism in schizophrenia.

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  • 1Genetic Unit, I.R.C.C.S. 'San Giovanni di Dio', A.Fa.R., Fatebenefratelli, Via Pilastroni 4, 25123 Brescia, Italy.


Association studies on gene polymorphisms of neurotransmitter systems have hypothesized an involvement of dopamine receptors in susceptibility to schizophrenia. However, structural and morphological abnormalities in different brain regions of schizophrenic patients support neurodevelopmental etiology for schizophrenia and neurotrophic factor genes could be candidates for genetic studies. The glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic and potential differentiation factor for dopaminergic systems. We have performed, in an Italian sample, an association study on 3' UTR (AGG)n repeat in GDNF gene. Our results have evidenced a difference in the allele frequencies between patients and controls (CLUMP (T1) chi2 = 17.365, df = 9, P = 0.043) and the (AGG)n > or = 15 alleles (Fisher Exact Test (two side) chi2 = 11.818, df = 1, P = 0.0003) were more present in the controls group. Similarity, the carriers of (AGG)n > or = 15 (OR = 0.176 95% CI: 0.060-0.520) were more present in the same group. These results support that the (AGG)n > or = 15 alleles could be protective factors against schizophrenia and thus they suggest a possible involvement of GDNF gene in the genetic liability to illness.

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