Association between MTHFR (677C>T and 1298A>C) polymorphisms and psychiatric disorder: A meta-analysis

Abstract

Recent studies showed that genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) is related to attention-deficit hyperactivity disorder (ADHD), bipolar disorder (BD) and schizophrenia (SCZ). However, no consistent conclusion has been determined. This meta-analysis aims to interrogate the relationship between MTHFR gene polymorphisms (677C>T and 1298A>C) and the occurrence of ADHD, BD and SCZ. We retrieved case-control studies that met the inclusion criteria from the PubMed database. Associations between MTHFR polymorphisms (677C>T and 1298A>C) and ADHD, BD and SCZ were measured by means of odds ratios (ORs) using a random effects model and 95% confidence intervals (CIs). Additionally, sensitivity analysis and publication bias were performed. After inclusion criteria were met, a total of five studies with ADHD including 434 cases and 670 controls, 18 studies with BD including 4167 cases and 5901 controls and 44 studies with SCZ including 16,098 cases and 19913 controls were finally included in our meta-analysis. Overall, our meta-analytical results provided evidence that the MTHFR 677C>T was associated with occurrence of BD and SCZ, while the 1298A>C polymorphism was related to ADHD and BD, and additionally the sensitivity analysis indicated these results were stable and reliable. This may provide useful information for relevant studies on the etiology of psychiatric disorders.

Fig 1. Flow of study identification, inclusion and exclusion.

Fig 2

Forest plot of the association between 667C>T variation and risk of ADHD in the five genetic models: A, allele contrast; B, homozygous codominant; C, heterozygous codominant; D, dominant; and E, recessive.

Fig 3

Forest plot of the associations between 1298A>C variation and risk of ADHD in the five genetic models: A, allele contrast; B, homozygous codominant; C, heterozygous codominant; D, dominant; and E, recessive.

Fig 4

Forest plot of the association between 667C>T variation and risk of bipolar disorder in the five genetic models: A, allele contrast; B, homozygous codominant; C, heterozygous codominant; D, dominant; and E, recessive.

Fig 5

Forest plot of the associations between 1298A>C variation and risk of bipolar disorder in the five genetic models: A, allele contrast; B, homozygous codominant; C, heterozygous codominant; D, dominant; and E, recessive.

Fig 6

Forest plot of the association between 667C>T variation and risk of schizophrenia in the five genetic models: A, allele contrast; B, homozygous codominant; C, heterozygous codominant; D, dominant; and E, recessive.

Fig 7

Forest plot of the associations between 1298A>C variation and risk of schizophrenia in the five genetic models: A, allele contrast; B, homozygous codominant; C, heterozygous codominant; D, dominant; and E, recessive.

Fig 8

Funnel plot analysis depicting publication bias in the association between MTHFR 677C>T polymorphism and ADHD in the five genetic models: A, allele contrast; B, homozygous codominant; C, heterozygous codominant; D, dominant; and E, recessive.

Fig 9

Funnel plot analysis depicting publication bias in the association between MTHFR 1298A>C polymorphism and ADHD in the five genetic models (A, allele contrast; B, homozygous codominant; C, heterozygous codominant; D, dominant; and E, recessive).

Fig 10

Funnel plot analysis depicting publication bias in the association between MTHFR 677C>T polymorphism and bipolar disorder in the five genetic models (A, allele contrast; B, homozygous codominant; C, heterozygous codominant; D, dominant; and E, recessive).

Fig 11

Funnel plot analysis depicting publication bias in the association between MTHFR 1298A>C polymorphism and bipolar disorder in the five genetic models (A, allele contrast; B, homozygous codominant; C, heterozygous codominant; D, dominant; and E, recessive).

Fig 12

Funnel plot analysis depicting publication bias in the association between MTHFR 677C>T polymorphism and schizophrenia in the five genetic models (A, allele contrast; B, homozygous codominant; C, heterozygous codominant; D, dominant; and E, recessive).

Fig 13

Funnel plot analysis depicting publication bias in the association between MTHFR 1298A>C polymorphism and schizophrenia in the five genetic models (A, allele contrast; B, homozygous codominant; C, heterozygous codominant; D, dominant; and E, recessive).