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

Published online by Cambridge University Press:  24 June 2014

Hwa-Young Lee  and
Yong-Ku Kim
Hwa-Young Lee
Affiliation:
Department of Psychiatry, College of Medicine, Korea University, Korea
Yong-Ku Kim*
Affiliation:
Department of Psychiatry, College of Medicine, Korea University, Korea Division of Brain Korea, 21 Biomedical Science, Korea University, Korea
*
Yong-Ku Kim, Department of Psychiatry, College of Medicine, Korea University Ansan Hospital, Ansan City, Gojan Dong, 516, Kyunggi Province 425-020, Korea. Tel: +82 31 412 5140; Fax: +82 31 412 5144; E-mail: [email protected]
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Abstract

Lee H-Y, Kim Y-K. 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.

Keywords

antipsychoticpolymorphismschizophreniatransforming growth factor-beta1treatment response
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 22 , Issue 4 , August 2010 , pp. 174 - 179
Copyright
Copyright © 2010 John Wiley & Sons A/S

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References

Dunn, AJ, Wang, J, Ando, T.Effects of cytokines on cerebral neurotransmission. Comparison with the effects of stress. Adv Exp Med Biol 1999;461:117–127. CrossRefGoogle ScholarPubMed
Leonard, BE.Changes in the immune system in depression and dementia: causal or co-incidental effects? Int J Dev Neurosci 2001;19:305–312. CrossRefGoogle ScholarPubMed
Krieglstein, K, Suter-Crazzolara, C, Fischer, WH, Unsicker, K.TGF-beta superfamily members promote survival of midbrain dopaminergic neurons and protect them against MPP+ toxicity. EMBO J 1995;14:736–742. CrossRefGoogle ScholarPubMed
Krieglstein, K, Unsicker, K.Transforming growth factor-beta promotes survival of midbrain dopaminergic neurons and protects them against N-methyl-4-phenylpyridinium ion toxicity. Neuroscience 1994;63:1189–1196. CrossRefGoogle ScholarPubMed
Zhang, L, Yi, H, Xia, XP, Zhao, Y.Transforming growth factor-beta: an important role in CD4+CD25+ regulatory T cells and immune tolerance. Autoimmunity 2006;39:269–276. CrossRefGoogle ScholarPubMed
Schmitt, E, Hoehn, P, Huels, Cet al. T helper type 1 development of naive CD4+ T cells requires the coordinate action of interleukin-12 and interferon-gamma and is inhibited by transforming growth factor-beta. Eur J Immunol 1994;24:793–798. CrossRefGoogle ScholarPubMed
Prud’homme, GJ, Piccirillo, CA.The inhibitory effects of transforming growth factor-beta-1 (TGF-beta1) in autoimmune diseases. J Autoimmun 2000;14:23–42. CrossRefGoogle ScholarPubMed
Barral-Netto, M, Barral, A, Brownell, CEet al. Transforming growth factor-beta in leishmanial infection: a parasite escape mechanism. Science 1992;257:545–548. CrossRefGoogle ScholarPubMed
Lindholm, D, Castren, E, Kiefer, R, Zafra, F, Thoenen, H.Transforming growth factor-beta 1 in the rat brain: increase after injury and inhibition of astrocyte proliferation. J Cell Biol 1992;117:395–400. CrossRefGoogle ScholarPubMed
Logan, A, Berry, M.Transforming growth factor-beta 1 and basic fibroblast growth factor in the injured CNS. Trends Pharmacol Sci 1993;14:337–342. CrossRefGoogle ScholarPubMed
Wahl, SM, Allen, JB, Mccartney-Francis, Net al. Macrophage- and astrocyte-derived transforming growth factor beta as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome. J Exp Med 1991;173:981–991. CrossRefGoogle ScholarPubMed
Horst, HA, Scheithauer, BW, Kelly, PJ, Kovach, JS.Distribution of transforming growth factor-beta 1 in human astrocytomas. Hum Pathol 1992;23:1284–1288. CrossRefGoogle ScholarPubMed
Morganti-Kossmann, MC, Kossmann, T, Wahl, SM.Cytokines and neuropathology. Trends Pharmacol Sci 1992;13: 286–291. CrossRefGoogle ScholarPubMed
Fujii, D, Brissenden, JE, Derynck, R, Francke, U.Transforming growth factor beta gene maps to human chromosome 19 long arm and to mouse chromosome 7. Somat Cell Mol Genet 1986;12:281–288. CrossRefGoogle ScholarPubMed
Francks, C, Tozzi, F, Farmer, Aet al. Population-based linkage analysis of schizophrenia and bipolar case-control cohorts identifies a potential susceptibility locus on 19q13. Mol Psychiatry 2008 [E-pub ahead of print].Google ScholarPubMed
Cambien, F, Ricard, S, Troesch, Aet al., The Etude Cas-Temoin de l’Infarctus du Myocarde (ECTIM) Study. Polymorphisms of the transforming growth factor-beta 1 gene in relation to myocardial infarction and blood pressure. Hypertension 1996;28:881–887. CrossRefGoogle ScholarPubMed
Hutchinson, IV, Turner, DM, Sankaran, D, Awad, MR, Sinnott, PJ.Influence of cytokine genotypes on allograft rejection. Transplant Proc 1998;30:862–863. CrossRefGoogle ScholarPubMed
Awad, MR, El-Gamel, A, Hasleton, P, Turner, DM, Sinnott, PJ, Hutchinson, IV.Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Transplantation 1998;66:1014–1020. CrossRefGoogle ScholarPubMed
Blobe, GC, Schiemann, WP, Lodish, HF.Role of transforming growth factor beta in human disease. N Engl J Med 2000;342:1350–1358. CrossRefGoogle ScholarPubMed
Vawter, MP, Dillon-Carter, O, Issa, F, Wyatt, RJ, Freed, WJ.Transforming growth factors beta 1 and beta 2 in the cerebrospinal fluid of chronic schizophrenic patients. Neuropsychopharmacology 1997;16:83–87. CrossRefGoogle ScholarPubMed
Vawter, MP, Dillon-Carter, O, Tourtellotte, WW, Carvey, P, Freed, WJ.TGFbeta1 and TGFbeta2 concentrations are elevated in Parkinson's disease in ventricular cerebrospinal fluid. Exp Neurol 1996;142:313–322. CrossRefGoogle ScholarPubMed
Lee, KM, Kim, YK.The role of IL-12 and TGF-beta1 in the pathophysiology of major depressive disorder. Int Immunopharmacol 2006;6:1298–1304. CrossRefGoogle ScholarPubMed
Kim, YK, Myint, AM, Lee, BHet al. T-helper types 1, 2, and 3 cytokine interactions in symptomatic manic patients. Psychiatry Res 2004;129:267–272. CrossRefGoogle Scholar
Na, KS, Kim, YK.Monocytic Th1 and th2 cytokine alterations in the pathophysiology of schizophrenia. Neuropsychobiology 2007;56:55–63. CrossRefGoogle ScholarPubMed
Kim, YK, Kim, L, Lee, MS.Relationships between interleukins, neurotransmitters and psychopathology in drug-free male schizophrenics. Schizophr Res 2000;44:165–175. CrossRefGoogle ScholarPubMed
Kim, YK, Lee, MS, Suh, KY.Decreased interleukin-2 production in Korean schizophrenic patients. Biol Psychiatry 1998;43:701–704. CrossRefGoogle ScholarPubMed
Kim, YK, Myint, AM, Lee, BHet al. Th1, Th2 and Th3 cytokine alteration in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2004;28:1129–1134. CrossRefGoogle ScholarPubMed
Woods, SW.Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry 2003;64: 663–667. CrossRefGoogle ScholarPubMed
Grainger, DJ, Heathcote, K, Chiano, Met al. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet 1999;8: 93–97. CrossRefGoogle ScholarPubMed
Suthanthiran, M, Li, B, Song, JOet al. Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: a novel mediator of hypertension and/or target organ damage. Proc Natl Acad Sci USA 2000;97: 3479–3484. Google ScholarPubMed
Sugiura, Y, Niimi, T, Sato, Set al. Transforming growth factor beta1 gene polymorphism in rheumatoid arthritis. Ann Rheum Dis 2002;61:826–828. CrossRefGoogle ScholarPubMed
Yamada, Y, Miyauchi, A, Goto, Jet al. Association of a polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis in postmenopausal Japanese women. J Bone Miner Res 1998;13:1569–1576. CrossRefGoogle ScholarPubMed
Yokota, M, Ichihara, S, Lin, TL, Nakashima, N, Yamada, Y.Association of a T29–>C polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to myocardial infarction in Japanese. Circulation 2000;101:2783–2787. CrossRefGoogle ScholarPubMed
Li, B, Khanna, A, Sharma, V, Singh, T, Suthanthiran, M, August, P.TGF-beta1 DNA polymorphisms, protein levels, and blood pressure. Hypertension 1999;33:271–275. CrossRefGoogle ScholarPubMed
Mors, O, Mortensen, PB, Ewald, H.A population-based register study of the association between schizophrenia and rheumatoid arthritis. Schizophr Res 1999;40:67–74. CrossRefGoogle ScholarPubMed
Leucht, S, Burkard, T, Henderson, J, Maj, M, Sartorius, N.Physical illness and schizophrenia: a review of the literature. Acta Psychiatr Scand 2007;116:317–333. CrossRefGoogle ScholarPubMed
Oken, RJ, Schulzer, M.At issue: schizophrenia and rheumatoid arthritis: the negative association revisited. Schizophr Bull 1999;25:625–638. CrossRefGoogle ScholarPubMed
Lee, EB, Kim, JY, Lee, YJ, Abdallah, A, Lympany, P, Song, YW.Transforming growth factor-beta1 polymorphisms in Korean patients with systemic sclerosis. Tissue Antigens 2004;63:491–495. CrossRefGoogle ScholarPubMed
Kim, Y, Lee, C.The gene encoding transforming growth factor beta 1 confers risk of ischemic stroke and vascular dementia. Stroke 2006;37:2843–2845. CrossRefGoogle ScholarPubMed
Lympany, PA, Avila, JJ, Mullighan, C, Marshall, S, Welsh, KI, Du Bois, RM.Rapid genotyping of transforming growth factor beta1 gene polymorphisms in a UK Caucasoid control population using the polymerase chain reaction and sequence-specific primers. Tissue Antigens 1998;52:573–578. CrossRefGoogle Scholar