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Tyrosine hydroxylase polymorphism and phenotypic heterogeneity in bipolar affective disorder: A multicenter association study

1999; Wiley; Volume: 88; Issue: 5 Linguagem: Inglês

10.1002/(sici)1096-8628(19991015)88

1096-8628

Daniel Souery, Olivier Lipp, Sarah K. Rivelli, Isabelle Massat, Alessandro Serretti, Maria Cristina Cavallini, Manfred Ackenheil, Rolf Adolfsson, H.N. Aschauer, Douglas Blackwood, Hans G. Dam, Dimitris Dikeos, S. Fuchshuber, Matthew G. Vander Heiden, Miro Jakovljević, Radka Kaneva, Lars Vedel Kessing, Bernard Lerer, Jouko Lnnqvist, T. Mellerup, Vihra Milanova, Walter Muir, P.-O. Nylander, Lilijana Oruč, G.N. Papadimitriou, P. Pekkarinen, Laura‐Maria Peltonen, C.B. Pull, P. Raeymaekers, Bracha Shapira, Enrico Smeraldi, Luc Staner, C. Stefanis, M. Verga, Geert R. Verheyen, Fabìo Macciardi, Christine Van Broeckhoven, Julien Mendlewicz,

Epigenetics and DNA Methylation

Tyrosine hydroxylase (TH), the rate-limiting enzyme in the metabolism of catecholamines, is considered a candidate gene in bipolar affective disorder (BPAD) and has been the subject of numerous linkage and association studies. Taken together, most results do not support a major gene effect for the TH gene in BPAD. Genetic and phenotypic heterogeneity may partially explain the difficulty of confirming the exact role of this gene using both association and linkage methods. Four hundred one BPAD patients and 401 unrelated matched controls were recruited within a European collaborative project (BIOMED1 project in the area of brain research, European Community grant number CT 92-1217, project leader: J. Mendlewicz) involving 14 centers for a case-control association study with a tetranucleotide polymorphism in the TH gene. Patients and controls were carefully matched for geographical origin. Phenotypic heterogeneity was considered and subgroup analyses were performed with relevant variables: age at onset, family history, and diagnostic stability. No association was observed in the total sample or for subgroups according to age at onset (n=172), family history alone (n=159), or high degree of diagnostic stability and a positive family history (n=131). The results of this association study do not confirm the possible implication of TH polymorphism in the susceptibility to BPAD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:527–532, 1999. © 1999 Wiley-Liss, Inc.