Association of tumor necrosis factor alpha gene -G308A polymorphism with schizophrenia

Sibylle Schwab, S. Mondabon, M. Knapp, M. Albus, J. Hallmayer, M. Borrmann-Hassenbach, M. Trixler, M. Gross, T.G. Schulze, M. Rietschel, B. Lerer, W. Maier, Dieter Wildenauer

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Background: Tumor necrosis factor alpha (TNFalpha), a cytokine involved in inflammatory processes, has been implicated in the pathophysiology of schizophrenia. The chromosomal location in the major histocompatibility complex (MHC) region on 6p21.1-21.3, a region with evidence for linkage, suggests a role in susceptibility to schizophrenia. Association of the minor (A) allele of the -G308A TNFa gene polymorphism with schizophrenia has been reported [Mol. Psychiatry 6 (2001) 79]. Methods: Association of the -G308A TNFalpha gene and the lymphotoxin alpha (LTalpha) + A252G gene polymorphisms with schizophrenia was studied in 79 sib pair families with linkage in the MHC region and in 128 trio families using the transmission disequilibrium test (TDT). Results: Weak association of the common G allele was detected for TNFalpha -G308A in both samples independently with borderline significance in the sib pair families (0.064) and with a nominally significant value of P = 0.022 in the trio families. Combining both samples produced P = 0.003, while LTalpha + A252G, located approximately 2-3 kb distally, revealed P = 0.03 and the two locus haplotype yielded a P value of 0.001. Conclusion: Our data suggests association of the common G allele of the -G308A TNFalpha gene polymorphism with schizophrenia in a sample of 207 families. However, linkage disequilibrium with a different allele of the TNFa gene or another gene in the MHC region cannot be excluded. (C) 2003 Elsevier Science B.V All rights reserved.
Original languageEnglish
Pages (from-to)19-25
JournalSchizophrenia Research
Issue number1
Publication statusPublished - 2003

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