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ID 109373
Title Alternative
統合失調症における性差を考慮した血中ホモシステイン濃度ならびにMTHFR遺伝子C677T多型の遺伝子関連研究のメタ解析
MTHFR, Homocysteine, and Schizophrenia
Author
Nishi, Akira The University of Tokushima
Tajima, Atsushi The University of Tokushima KAKEN Search Researchers
Kikuchi, Kumiko The University of Tokushima
Shimodera, Shinji Kochi University
Ohi, Kazutaka Osaka University
Hashimoto, Ryota Osaka University
Imoto, Issei The University of Tokushima KAKEN Search Researchers
Takeda, Masatoshi Osaka University
Keywords
mendelian randomization
SNP
Japanese
plasma homocysteine
Content Type
Thesis or Dissertation
Description
Previous studies suggest that elevated blood homocysteine levels and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism are risk factors for schizophrenia. However, the effects of gender and MTHFR C677T genotypes on blood homocysteine levels in schizophrenia have not been consistent. We first investigated whether plasma total homocysteine levels were higher in patients with schizophrenia than in controls with stratification by gender and by the MTHFR C677T genotypes in a large cohort (N = 1379). Second, we conducted a meta-analysis of association studies between blood homocysteine levels and schizophrenia separately by gender (N = 4714). Third, we performed a case-control association study between the MTHFR C677T polymorphism and schizophrenia (N = 4998) and conducted a meta-analysis of genetic association studies based on Japanese subjects (N = 10 378). Finally, we assessed the effect of plasma total homocysteine levels on schizophrenia by a mendelian randomization approach. The ANCOVA after adjustment for age demonstrated a significant effect of diagnosis on the plasma total homocysteine levels in all strata, and the subsequent meta-analysis for gender demonstrated elevated blood homocysteine levels in both male and female patients with schizophrenia although antipsychotic medication might influence the outcome. The meta-analysis of the Japanese genetic association studies demonstrated a significant association between the MTHFR C677T polymorphism and schizophrenia. The mendelian randomization analysis in the Japanese populations yielded an OR of 1.15 for schizophrenia per 1-SD increase in plasma total homocysteine. Our study suggests that increased plasma total homocysteine levels may be associated with an increased risk of schizophrenia.
Journal Title
Schizophrenia Bulletin
ISSN
17451701
05867614
NCID
AA12096330
AA00441500
Publisher
Maryland Psychiatric Research Center|Oxford University Press
Volume
40
Issue
5
Start Page
1154
End Page
1163
Published Date
2014-02-17
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201505251007.pdf
論文本文 : LID201505251008.pdf
本論文は, 著者Akira Nishiの学位論文として提出され, 学位審査・授与の対象となっている。
Rights
© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第2805号
Diploma Number
甲医第1247号
Granted Date
2015-03-23
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
University Hospital