Effect of TGF-β1 polymorphism on the susceptibility to schizophrenia and treatment response to atypical antipsychotic agent

Objective: Several studies have suggested that cytokine alterations could be related to the pathophysiology of schizophrenia. Transforming growth factor-beta1 (TGF-β1) is believed to be an important factor in regulation of inflammatory responses and to have anti-inflammatory effects. TGF-β1 also has trophic effects on dopaminergic neurons. We tested the hypothesis TGF-β1 is associated with the pathophysiology of schizophrenia. Methods: The polymorphisms at codon 10 (T869C) and codon 25 (G915C) of TGF-β1 were analysed in 99 schizophrenia patients and 130 normal controls. At baseline and after 8 weeks of treatment, clinical symptoms were evaluated on Positive and Negative Syndrome Scale (PANSS). Results: None of the subjects were polymorphic at codon 25. However, the C allele at codon 10 was more frequent in schizophrenia (p = 0.05). Although schizophrenia group showed a higher tendency of allele frequency in the subjects with C allele (p = 0.05), the allelic difference did not reach statistical significance after correction for multiple comparisons (p = 0.1). PANSS scores showed no significant correlation with genotypes. The genotype distribution was not significantly different between responders and non-responders. However, the C allele was more frequent among responders (p = 0.03). Conclusion: These results suggest that the TGF-β1 polymorphism is associated with therapeutic response to antipsychotics. However, further studies with larger numbers of subjects are needed to confirm the effect of TGF-β1 in schizophrenia.