Journal of Neural Transmission

, Volume 122, Issue 2, pp 307–320 | Cite as

Methylenetetrahydrofolate reductase (MTHFR) polymorphism susceptibility to schizophrenia and bipolar disorder: an updated meta-analysis

  • Cai-Yun Hu
  • Zhen-Zhong Qian
  • Feng-Feng Gong
  • Shan-Shan Lu
  • Fang Feng
  • Yi-Le Wu
  • Hui-Yun Yang
  • Ye-Huan Sun
Psychiatry and Preclinical Psychiatric Studies - Original Article


Previous studies examining the possible role of the methylenetetrahydrofolate reductase (MTHFR) polymorphisms in the development of schizophrenia (SZ) and bipolar disorder (BPD) have provided inconclusive findings, this meta-analysis was therefore designed to get a more reliable assessment. A total of 38 articles were identified through a search of electronic databases, up to 27 February 2014. Odds ratios (ORs) with 95 % confidence interval (CIs) were calculated using random effects models. Meta-analysis showed that MTHFR C677T was significantly associated with SZ, the highest OR was found for the recessive model (for TT vs. CT + CC: OR = 1.34, 95 % CI: 1.18–1.53); a marginal association of MTHFR C677T with increased risk of BPD has also been found for the recessive model (OR = 1.26, 95 % CI: 1.00–1.59). Subgroup analysis by ethnicity indicated that the significant association with SZ and BPD existed among Asian and African populations, but not for the white. MTHFR A1298C was significant associated with SZ, the highest OR for the dominant model (OR = 1.13, 95 % CI: 1.03–1.24). Subgroup analysis indicated a significant association with SZ existed in Asian populations, not among the white populations and no significant association was detected between the MTHFR A1298C and BPD in all groups. We conclude that MTHFR polymorphism is associated with SZ and BPD among Asian, African populations, but not the white.


Methylenetetrahydrofolate reductase MTHFR Polymorphism Schizophrenia Bipolar disorder Meta-analysis 



This study was supported by National Natural Science Foundation of China (81172763).

Conflict of interest



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Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Cai-Yun Hu
    • 1
  • Zhen-Zhong Qian
    • 1
  • Feng-Feng Gong
    • 1
  • Shan-Shan Lu
    • 1
  • Fang Feng
    • 1
  • Yi-Le Wu
    • 1
  • Hui-Yun Yang
    • 1
  • Ye-Huan Sun
    • 1
    • 2
  1. 1.Department of Epidemiology and Health StatisticsSchool of Public Health, Anhui Medical UniversityHefeiChina
  2. 2.Centre for Evidence-Based PracticeAnhui Medical UniversityHefeiChina

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