CAJ | 학술논문

目的评价亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR) C677T基因多态性与精神分裂症的遗传关联性.方法通过维普中国科技期刊数据库、中国期刊全文数据库、万方数字化期刊全文数据库以及PubMed、Embase、SchizophreniaGene和HuGENet,并辅以文献溯源方法检索有关MTHFR C677T基因多态性与精神分裂症风险的病例对照试验文献,依照事先定义的纳入及排除标准进行筛选,并根据基因关联性研究的报告标准评价文献质量.以Meta分析法评价该位点基因多态性的优势比(odds ratio,OR),并作Meta回归和亚组分析.结果共纳入28篇合格文献(病例组7 257例,对照组8 900例),中～高度异质性.Meta分析显示,全部人群中T等位基因(OR=1.15,Z=3.53,P=0.000)、TT基因型(OR=1.37,Z=3.63,P=0.000)均增加精神分裂症易感风险,差异有统计学意义;CT基因型稍增加精神分裂症的风险,但差异无统计学意义(OR=1.10;Z=1.86,P=0.064).Meta回归显示,中国人群研究约占全部异质性来源的68.74％(t=3.69,P=0.001).亚组分析显示,TT基因型在中国亚组(OR=4.12,Z=5.27,P=O.000)和非中国亚组(OR=1.25,Z=2.92,P=0.003)、CT基因型在中国亚组(OR=2.18,Z=3.84,P=0.000)增加精神分裂症风险,性别分层提示只有携带TT基因型的男性亚组增加精神分裂症风险(OR=1.51,Z=2.55,P=0.011).累积Meta分析和敏感性分析显示,结论较为稳健(受影响最大时OR=1.31,95％可信区间1.12～1.53).Begg's检验(Z=1.46,P=O.143)和Egger's检验(t=1.96,P=0.060)显示无明显发表偏倚.结论 MTHFR C677T基因多态性与精神分裂症存在遗传关联性,不同性别、地域和种族间存在较大差异.
목적 평개아갑기사경협산환원매(methylenetetrahydrofolate reductase,MTHFR) C677T기인다태성여정신분렬증적유전관련성.방법 통과유보중국과기기간수거고、중국기간전문수거고、만방수자화기간전문수거고이급PubMed、Embase、SchizophreniaGene화HuGENet,병보이문헌소원방법검색유관MTHFR C677T기인다태성여정신분렬증풍험적병례대조시험문헌,의조사선정의적납입급배제표준진행사선,병근거기인관련성연구적보고표준평개문헌질량.이Meta분석법평개해위점기인다태성적우세비(odds ratio,OR),병작Meta회귀화아조분석.결과 공납입28편합격문헌(병례조7 257례,대조조8 900례),중～고도이질성.Meta분석현시,전부인군중T등위기인(OR=1.15,Z=3.53,P=0.000)、TT기인형(OR=1.37,Z=3.63,P=0.000)균증가정신분렬증역감풍험,차이유통계학의의;CT기인형초증가정신분렬증적풍험,단차이무통계학의의(OR=1.10;Z=1.86,P=0.064).Meta회귀현시,중국인군연구약점전부이질성래원적68.74％(t=3.69,P=0.001).아조분석현시,TT기인형재중국아조(OR=4.12,Z=5.27,P=O.000)화비중국아조(OR=1.25,Z=2.92,P=0.003)、CT기인형재중국아조(OR=2.18,Z=3.84,P=0.000)증가정신분렬증풍험,성별분층제시지유휴대TT기인형적남성아조증가정신분렬증풍험(OR=1.51,Z=2.55,P=0.011).루적Meta분석화민감성분석현시,결론교위은건(수영향최대시OR=1.31,95％가신구간1.12～1.53).Begg's검험(Z=1.46,P=O.143)화Egger's검험(t=1.96,P=0.060)현시무명현발표편의.결론 MTHFR C677T기인다태성여정신분렬증존재유전관련성,불동성별、지역화충족간존재교대차이.
Objective To evaluate the hereditary relation of genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR)C677T with the risk of schizophrenia.Methods According to established strategy and selection criteria and exclusion criteria,a search had been performed on Chinese Wanfang Database,Chinese National Knowledge Infrastructure and Database,Chongqing VIP Database for Chinese Technical Periodicals,PubMed,Embase,Schizophrenia-Gene and HuGENet to identify all the case-control studies associated with MTHFR C677T genetic polymorphisms and schizophrenia.Hand searches of cross references were also conducted for further references.The quality of included studies was evaluated by Strengthening the Reporting of Genetic Association Studies (STREGA).In addition to common meta-analysis,cumulative meta-analysis,regressive meta-analysis,subgroup analysis,sensitive analysis and publication bias testing were used to analyze the data.Results Twenty-eight eligible studies with moderate to obvious heterogeneity were included,involving total 7 257 cases and 8 900 controls.There were significant associations between C677T polymorphisms and schizophrenia risk throughout whole populations by T-allele vs.C-allele (odds ratio,OR; OR =1.15,Z =3.53,P =0.000) and by TT-genotype vs.CCgenotype (OR =1.37,Z =3.63,P =0.000),but not by CT-genotype vs.CC-genotype (OR =1.10,Z =1.86,P =0.064).Since the regressive meta-analysis demonstrated most studies from China accounted for the whole heterogeneity by 68.74％ (t =3.69,P =0.001),a further subgroup-analysis was carried out to show that TT-genotype relative to CC-genotype led to significantly higher risks of schizophrenia throughout the Chinese-subgroup(OR =4.12,Z =5.27,P =0.000) and non-Chinese subgroup(OR =1.25,Z =2.92,P =0.003),while CT-genotype only in Chinese-subgroup (OR =2.18,Z =3.84,P =0.000).As stratified by gender,only male-subgroup who carried TT-genotype represented a significant association (TT vs.CC:OR =1.51,Z =2.55,P =0.011).The performed meta-analyses showed consistent results to cumulative meta-analysis and sensitive analysis,and no evidence of publication bias by Begg's test (Z =1.46,P =0.143) and Egger's test (t =1.96,P =0.060).Conclusion The study provides evidence for a hereditary associations between the MTHFR C677T variant and schizophrenia risk,however it is obviously various between different regions,ethnicities and genders.