Association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and age of onset in schizophrenia.

Autor: Vares M; Department of Clinical Neuroscience, HUBIN project, Karolinska Institutet and Hospital, Stockholm, Sweden., Saetre P; Department of Clinical Neuroscience, HUBIN project, Karolinska Institutet and Hospital, Stockholm, Sweden., Deng H; Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China., Cai G; Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, New York., Liu X; Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China., Hansen T; Research Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark., Rasmussen HB; Research Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark., Werge T; Research Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark., Melle I; Institute of Psychiatry, University of Oslo, Oslo, Norway.; Department Psychiatry, Oslo University Hospital, Ullevål, Oslo, Norway., Djurovic S; Institute of Psychiatry, University of Oslo, Oslo, Norway.; Department of Medical Genetics, Oslo University Hospital, Ullevål, Oslo, Norway., Andreassen OA; Institute of Psychiatry, University of Oslo, Oslo, Norway.; Department Psychiatry, Oslo University Hospital, Ullevål, Oslo, Norway., Agartz I; Department of Clinical Neuroscience, HUBIN project, Karolinska Institutet and Hospital, Stockholm, Sweden.; Institute of Psychiatry, University of Oslo, Oslo, Norway.; Department of Psychiatry, Section Vinderen, University of Oslo, Oslo, Norway., Hall H; Department of Clinical Neuroscience, HUBIN project, Karolinska Institutet and Hospital, Stockholm, Sweden.; Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden., Terenius L; Department of Clinical Neuroscience, HUBIN project, Karolinska Institutet and Hospital, Stockholm, Sweden., Jönsson EG; Department of Clinical Neuroscience, HUBIN project, Karolinska Institutet and Hospital, Stockholm, Sweden.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics [Am J Med Genet B Neuropsychiatr Genet] 2010 Mar 05; Vol. 153B (2), pp. 610-618.
DOI: 10.1002/ajmg.b.31030
Abstrakt: Different lines of evidence indicate that methylenetetrahydrofolate reductase (MTHFR) functional gene polymorphisms, causative in aberrant folate-homocysteine metabolism, are associated with increased vulnerability to several heritable developmental disorders. Opposing views are expressed considering the possible association between MTHFR and susceptibility for schizophrenia. In order to evaluate if age of onset could explain some of this discrepancy we investigated the relationship between two functional MTHFR gene polymorphisms and age at onset in this disorder. Scandinavian patients (n = 820) diagnosed with schizophrenia, schizoaffective disorder, and schizophreniform disorder were investigated. Two functional MTHFR single nucleotide polymorphisms (SNPs; rs1801131 and rs1801133) were genotyped and the effect of MTHFR polymorphisms on the age of onset was examined with survival analysis. In an attempt to replicate the findings from the Scandinavian sample, the association between rs1801133 and age at onset was also analyzed in Chinese high-risk families, with two or more affected siblings (n = 243). Among the Scandinavian patients the functional MTHFR SNP rs1801133 (C677T) significantly affected age at onset of schizophrenia in a dose-dependent manner (P = 0.0015), with lower age of onset with increasing numbers of the mutant T-allele. There was no evidence of rs1801131 (A1298C) affecting age of onset in schizophrenia. Within the Chinese high-risk families carriers of the MTHFR 677T allele showed earlier age at onset than siblings being homozygous for the wild-type allele (P = 0.008). The MTHFR C677T polymorphism may play a role as a modifying factor for age of onset in schizophrenia.
((c) 2009 Wiley-Liss, Inc.)
Databáze: MEDLINE
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