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.

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.

Objective To evaluate the association between methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and depression risk.Methods Available studies containing genotype frequencies of MTHFR C677T were chosen,and pooled odds ratio (OR) with 95％ confidence interval (CI) was used to assess the strength of the association.Results Twenty-five eligible studies including 4 048 cases and 12 827 controls were identified.Meta-analysis showed a significant effect in the co-dominant model (T vs.C:OR 0 =1.25; Z=3.82,P=0.000;TTvs.CC:OR1=1.55,Z=3.79,P=0.000 ; except CT vs.CC:OR2=1.13; Z=1.78,P=0.076).Stratified analysis denoted that there was significantly higher risk in depression onset before 60 years old than depression onset after 60 years old.In subgroup analysis stratified by regressive meta-analysis,MTHFR C677T variant was statistically significantly relevant to depression risk in Chinese populations (OR 0 =1.58,Z=3.95,P=0.000; OR 1 =2.55,Z=3.92,P=0.000; OR 2 =1.43,Z=2.72,P=0.007),but not in no-Chinese populations (OR 0 =1.12,Z=2.10,P=0.035 ; OR 1 =1.23,Z=2.23,P=0.025 ; OR 2 =1.06,Z=0.74,P=0.456).Evidentiary strength rated by GRADE showed that 1 study moderate,3 studies low and 7 stdudies very low.Conclusion Our study provides evidence for a hereditary association between the MTHFR C677T variant and depression susceptibility,whereas there is an obvious variety in different regions,ethnicities and onset age.