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タイトル別表記
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
著者
西, 晃 徳島大学大学院医科学教育部(医学専攻)
田嶋, 敦 The University of Tokushima KAKEN研究者をさがす
Kikuchi, Kumiko The University of Tokushima
Shimodera, Shinji Kochi University
Ohi, Kazutaka Osaka University
Hashimoto, Ryota Osaka University
井本, 逸勢 The University of Tokushima KAKEN研究者をさがす
Takeda, Masatoshi Osaka University
キーワード
mendelian randomization
SNP
Japanese
plasma homocysteine
資料タイプ
学位論文
抄録
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.
掲載誌名
Schizophrenia Bulletin
ISSN
17451701
05867614
cat書誌ID
AA12096330
AA00441500
出版者
Maryland Psychiatric Research Center|Oxford University Press
40
5
開始ページ
1154
終了ページ
1163
発行日
2014-02-17
備考
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。
権利情報
© 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
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第2805号
学位記番号
甲医第1247号
学位授与年月日
2015-03-23
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院