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

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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Abstract

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.

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References

  • Ades AE, Lu G, Higgins JP (2005) The interpretation of random-effects meta-analysis in decision models. Med Decis Making 25:646–654

    Article  CAS  PubMed  Google Scholar 

  • Angst J, Gamma A, Lewinsohn P (2002) The evolving epidemiology of bipolar disorder. World Psychiatry 1:146–148

    PubMed Central  PubMed  Google Scholar 

  • Arinami T, Yamada N, Yamakawa-Kobayashi K, Hamaguchi H, Toru M (1997) Methylenetetrahydrofolate reductase variant and schizophrenia/depression. Am J Med Genet 74:526–528

    Article  CAS  PubMed  Google Scholar 

  • Arzaghi SM, Hossein-Nezhad A, Shariat SV, Ghodsipour A, Shams J, Larijani B (2011) C677T Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphism in Schizophrenia and Bipolar Disorder: an Association Study in Iranian Population. Iran J Psychiatry 6:1–6

    PubMed Central  PubMed  Google Scholar 

  • Betcheva ET, Mushiroda T, Takahashi A, Kubo M, Karachanak SK et al (2009) Case-control association study of 59 candidate genes reveals the DRD2 SNP rs6277 (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian population. J Hum Genet 54:98–107

    Article  CAS  PubMed  Google Scholar 

  • Bouaziz N, Ayedi I, Sidhom O, Kallel A, Rafrafi R, Zaharieva IT, Vazharova RV, Dimova II, Milanova VK, Tolev T, Kirov G, Owen MJ, O’Donovan MC, Kamatani N, Nakamura Y, Toncheva DI (2010) Plasma homocysteine in schizophrenia: determinants and clinical correlations in Tunisian patients free from antipsychotics. Psychiatry Res 179:24–29

    Article  CAS  PubMed  Google Scholar 

  • Chen Z, Liu Y, Zhang D, Liu Z, Wang P, Zhou D, Zhao T, Wang T, Xu H, Li S, Feng G, He L, Yu L (2009) C677T methylenetetrahydrofolate reductase gene polymorphisms in bipolar disorder: an association study in the Chinese population and a meta-analysis of genetic association studies. Neurosci Lett 449:48–51

    Article  CAS  PubMed  Google Scholar 

  • Cohen-Woods S, Craig I, Gaysina D, Gray J, Gunasinghe C, Craddock N (2010) The Bipolar Association Case-Control Study (BACCS) and meta-analysis: no association with the 5,10-methylenetetrahydrofolate reductase gene and bipolar disorder. Am J Med Genet Part B Neuropsychiatr Genet 153B:1298–1304

    Article  CAS  Google Scholar 

  • del Rio GC, Torres-Sánchez L, Chen J, Schnaas L, Hernández C, Osorio E, Portillo MG, Lopez-Carrillo L (2009) Maternal MTHFR 677C > T genotype and dietary intake of folate and vitamin B(12): their impact on child neurodevelopment. Nutr Neurosci 12:13–20

    Article  Google Scholar 

  • DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  CAS  PubMed  Google Scholar 

  • Dror DK, Allen LH (2008) Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms. Nutr Rev 66:250–255

    Article  PubMed  Google Scholar 

  • Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • El-Hadidy MA, Abdeen HM, El-Aziz SMA, Al-Harrass M (2013) C677T Methylenetetrahydrofolate reductase gene polymorphism in schizophrenia and bipolar disorder. Psychiatric Genetics (Epub ahead of print)

  • Ezzaher A, Mouhamed DH, Mechri A, Omezzine A, Neffati F, Douki W, Bouslama A, Gaha L, Najjar MF (2011) Hyperhomocysteinemia in Tunisian bipolar I patients. Psychiatry Clin Neurosci 65:664–671

    Article  PubMed  Google Scholar 

  • Feng LG, Song ZW, **n F, Hu J (2009) Association of plasma homocysteine and methylenetetrahydrofolate reductase C677T gene variant with schizophrenia: a Chinese Han population-based case-control study. Psychiatry Res 168:205–208

    Article  CAS  PubMed  Google Scholar 

  • Fleiss JL, Gross AJ (1991) Meta-analysis in epidemiology, with special reference to studies of the association between exposure to environmental tobacco smoke and lung cancer: a critique. J Clin Epidemiol 44:127–139

    Article  CAS  PubMed  Google Scholar 

  • Frankenburg FR (2007) The role of one-carbon metabolism in schizophrenia and depression. Harv Rev Psychiatry 15:146–160

    Article  PubMed  Google Scholar 

  • Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP, Rozen R (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Miss Mdel R, Perez-Mutul J, Lopez-Canul B, Solis-Rodriguez F, Puga-Machado L, Oxte-Cabrera A, Gurubel-Maldonado J, Arankowsky-Sandoval G (2010) Folate, homocysteine, interleukin-6, and tumor necrosis factor alpha levels, but not the methylenetetrahydrofolate reductase C677T polymorphism, are risk factors for schizophrenia. J Psychiatr Res 44:441–446

    Article  PubMed  Google Scholar 

  • Gilbody S, Lewis S, Lightfoot T (2007) Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review. Am J Epidemiol 165:1–13

    Article  PubMed  Google Scholar 

  • Goyette P, Pai A, Milos R, Frosst P, Tran P, Chen Z, Chan M, Rozen R (1998) Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR). Mamm Genome 9:652–656

    Article  CAS  PubMed  Google Scholar 

  • Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  • Jonsson EG, Larsson K, Vares M, Hansen T, Wang AG, Djurovic S, Rønningen KS, Andreassen OA, Agartz I, Werge T, Terenius L, Hall H (2008) Two methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, schizophrenia and bipolar disorder: an association study. Am J Med Genet B Neuropsychiatr Genet 147B:976–982

    Article  PubMed  Google Scholar 

  • Joober R, Benkelfat C, Lal S, Bloom D, Labelle A, Lalonde P, Turecki G, Rozen R, Rouleau GA (2000) Association between the methylenetetrahydrofolate reductase 677C– > T missense mutation and schizophrenia. Mol Psychiatry 5:323–326

    Article  CAS  PubMed  Google Scholar 

  • Kang HJ, Choe BM, Kim SH, Son S, Lee K, Kim BG, Hong Y (2010) No association between functional polymorphisms in COMT and MTHFR and schizophrenia risk in Korean population. Epidemiol Health 32:1–7

    Google Scholar 

  • Kempisty B, Mostowska A, Gorska I, Luczak M, Czerski P, Szczepankiewicz A, Hauser J, Jagodziński PP (2006) Association of 677C > T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene with bipolar disorder and schizophrenia. Neurosci Lett 400:267–271

    Article  CAS  PubMed  Google Scholar 

  • Kempisty B, Bober A, Łuczak M, Czerski P, Szczepankiewicz A, Hauser J, Jagodzinski PP (2007) Distribution of 1298A > C polymorphism of methylenetetrahydrofolate reductase gene in patients with bipolar disorder and schizophrenia. Eur Psychiatry 22:39–43

    Article  PubMed  Google Scholar 

  • Kim SG, Song JY, Joo EJ, Jeong SH, Kim SH, Lee KY, Lee NY, Ahn YM, Kim YS, Roh MS (2011) No association of functional polymorphisms in methlylenetetrahydrofolate reductase and the risk and minor physical anomalies of schizophrenia in Korean population. J Korean Med Sci 26:1356–1363

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kontis D, Theochari E, Fryssira H, Kleisas S, Sofocleous C, Andreopoulou A, Kalogerakou S, Gazi A, Boniatsi L, Chaidemenos A, Tsaltas E (2013) COMT and MTHFR polymorphisms interaction on cognition in schizophrenia: an exploratory study. Neurosci Lett 537:17–22

    Article  CAS  PubMed  Google Scholar 

  • Krebs MO, Bellon A, Mainguy G, Jay TM, Frieling H (2009) One-carbon metabolism and schizophrenia: current challenges and future directions. Trends Mol Med 15:562–570

    Article  CAS  PubMed  Google Scholar 

  • Kunugi H, Fukuda R, Hattori M, Kato T, Tatsumi M, Sakai T, Hirose T, Nanko S (1998) C677T polymorphism in methylenetetrahydrofolate reductase gene and psychoses. Mol Psychiatry 3:435–437

    Article  CAS  PubMed  Google Scholar 

  • Lee YS, Han DH, Jeon CM, Lyoo IK, Na C, Chae SL, Cho SC (2006) Serum homocysteine, folate level and methylenetetrahydrofolate reductase 677, 1298 gene polymorphism in Korean schizophrenic patients. Neuroreport 17:743–746

    Article  CAS  PubMed  Google Scholar 

  • Muntjewerff JW, Ophoff RA, Buizer-Voskamp JE, Strengman E, den Heijer M, GROUP Consortium (2011) Effects of season of birth and a common MTHFR gene variant on the risk of schizophrenia. Eur Neuropsychopharmacol 21:300–305

    Article  CAS  PubMed  Google Scholar 

  • Muntjewerff JW, Gellekink H, den Heijer M, Hoogendoorn ML, Kahn RS, Sinke RJ, Blom HJ (2008) Polymorphisms in catechol-O-methyltransferase and methylenetetrahydrofolate reductase in relation to the risk of schizophrenia. Eur Neuropsychopharmacol 18:99–106

    Article  CAS  PubMed  Google Scholar 

  • Nishi A, Numata S, Tajima A, Kinoshita M, Kikuchi K, Shimodera S, Tomotake M, Ohi K, Hashimoto R, Imoto I, Takeda M, Ohmori T (2014) Meta-analyses of blood homocysteine levels for gender and genetic association studies of the MTHFR C677T polymorphism in schizophrenia. Schizophr Bull [Epub ahead of print]

  • Ozbek Z, Kucukali CI, Ozkok E, Orhan N, Aydin M, Kilic G, Sazci A, Kara I (2008) Effect of the methylenetetrahydrofolate reductase gene polymorphisms on homocysteine, folate and vitamin B12 in patients with bipolar disorder and relatives. Prog Neuropsychopharmacol Biol Psychiatry 32:1331–1337

    Article  CAS  PubMed  Google Scholar 

  • Peerbooms OL, van Os J, Drukker M, Kenis G, Hoogveld L, MTHFR in Psychiatry Group, de Hert M, Delespaul P, van Winkel R, Rutten BP (2011) Meta-analysis of MTHFR gene variants in schizophrenia, bipolar disorder and unipolar depressive disorder: evidence for a common genetic vulnerability? Brain Behav Immun 25:1530–1543

    Article  CAS  PubMed  Google Scholar 

  • Philibert R, Gunter T, Hollenbeck N, Adams WJ, Bohle P, Packer H, Sandhu H (2006) No association of the C677T methylenetetrahydrofolate reductase polymorphism with schizophrenia. Psychiatr Genet 16:221–223

    Article  PubMed  Google Scholar 

  • Purcell SM, Wray NR, Stone JL, Visscher PM, O’Donovan MC, Sullivan PF, Sklar P (2009) Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460:748–752

    CAS  PubMed  Google Scholar 

  • Rai V (2011) Evaluation of methylenetetrahydrofolate reductase gene variant (C677T) as risk factor for bipolar disorder. Cell Mol Biol (Noisy-le-grand) 57(Suppl):Ol1558–Ol1566

    CAS  Google Scholar 

  • Reif A, Pfuhlmann B, Lesch KP (2005) Homocysteinemia as well as methylenetetrahydrofolate reductase polymorphism are associated with affective psychoses. Prog Neuropsychopharmacol Biol Psychiatry 29:1162–1168

    Article  CAS  PubMed  Google Scholar 

  • Roffman JL, Gollub RL, Calhoun VD, Wassink TH, Weiss AP, Ho BC, White T, Clark VP, Fries J, Andreasen NC, Goff DC, Manoach DS (2008) MTHFR 677C > T genotype disrupts prefrontal function in schizophrenia through an interaction with COMT 158Val – > Met. Proc Natl Acad Sci USA 105:17573–17578

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Saetre P, Vares M, Werge T, Andreassen OA, Arinami T, Ishiguro H, Nanko S, Tan EC, Han DH, Roffman JL, Muntjewerff JW, Jagodzinski PP, Kempisty B, Hauser J, Vilella E, Betcheva E, Nakamura Y, Regland B, Agartz I, Hall H, Terenius L, Jönsson EG (2011) Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and age of onset in schizophrenia: a combined analysis of independent samples. Am J Med Genet B Neuropsychiatr Genet 156:215–224

    Article  PubMed  Google Scholar 

  • Saha S, Chant D, Welham J, McGrath J (2005) A systematic review of the prevalence of schizophrenia. PLoS Med 2:413–433

    Article  Google Scholar 

  • Sazci A, Ergül E, Güzelhan Y, Kaya G, Kara I (2003) Methylenetetrahydrofolate reductase gene polymorphisms in patients with schizophrenia. Mol Brain Res 117:104–107

    Article  CAS  PubMed  Google Scholar 

  • Sazci A, Ergul E, Kucukali I, Kara I, Kaya G (2005) Association of the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene with schizophrenia: association is significant in men but not in women. Prog Neuropsychopharmacol Biol Psychiatry 29:1113–1123

    Article  CAS  PubMed  Google Scholar 

  • Sugden C (2006) One-carbon metabolism in psychiatric illness. Nutr Res Rev 19:117–136

    Article  CAS  PubMed  Google Scholar 

  • Tan EC, Chong SA, Lim LC, Chan AO, Teo YY, Tan CH, Mahendran R (2004) Genetic analysis of the thermolabile methylenetetrahydrofolate reductase variant in schizophrenia and mood disorders. Psychiatr Genet 14:227–231

    Article  PubMed  Google Scholar 

  • Tsuang M (2000) Schizophrenia: genes and environment. Biol Psychiatry 47:210–220

    Article  CAS  PubMed  Google Scholar 

  • Tsutsumi A, Glatt SJ, Kanazawa T, Kawashige S, Uenishi H, Hokyo A, Kaneko T, Moritani M, Kikuyama H, Koh J, Matsumura H, Yoneda H (2011) The genetic validation of heterogeneity in schizophrenia. Behav Brain Funct 7:43

    Article  PubMed Central  PubMed  Google Scholar 

  • van der Put NM, Gabreels F, Stevens EM, Smeitink JA, Trijbels FJ, Eskes TK, van den Heuvel LP, Blom HJ (1998) A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet 62:1044–1051

    Article  PubMed Central  PubMed  Google Scholar 

  • van der Put NM, van Straaten HW, Trijbels FJ, Blom HJ (2001) Folate, homocysteine and neural tube defects: an overview. Exp Biol Med (Maywood) 226:243–270

    Google Scholar 

  • Vilella E, Virgos C, Murphy M, Martorell L, Valero J, Simo JM, Joven J, Fernández-Ballart J, Labad A (2005) Further evidence that hyperhomocysteinemia and methylenetetrahydrofolate reductase C677T and A1289C polymorphisms are not risk factors for schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 29:1169–1174

    Article  CAS  PubMed  Google Scholar 

  • Virgos C, Martorell L, Simo JM, Valero J, Figuera L, Joven J, Labad A, Vilella E (1999) Plasma homocysteine and the methylenetetrahydrofolate reductase C677T gene variant: lack of association with schizophrenia. Neuroreport 10:2035–2038

    Article  CAS  PubMed  Google Scholar 

  • Wu YL, Ding XX, Sun YH, Yang HY, Chen J, Zhao X, Jiang YH, Lv XL, Wu ZQ (2013) Association between MTHFR C677T polymorphism and depression: an updated meta-analysis of 26 studies. Prog Neuropsychopharmacol Biol Psychiatry 46:78–85

    Article  CAS  PubMed  Google Scholar 

  • Yang DY, Lu XB, Li YH, Tong ZS, Fu Y, Yang MX, Huang P (2007) The association between MTHFR and Blood Homocysteine Levels in first-episode schizophrenia. Chin J Behav Med Sci 16:901–902 (Chinese)

    CAS  Google Scholar 

  • Yang Z, Zhang XF, Liu HX, Hao YS, Zhao CL (2012) MTHFR C677T polymorphism and colorectal cancer risk in Asians, a meta-analysis of 21 studies. Asian Pac J Cancer Prev 13:1203–1211

    Article  PubMed  Google Scholar 

  • Ye XM, Zhang X, Wang HL (2010) Association between the MTHFR gene polymorphisms and schizophrenia. Hei Long Jiang Medial Joural 34:641–645 (Chinese)

    Google Scholar 

  • Yu L, Li T, Robertson Z, Dean J, Gu NF, Feng GY, Yates P, Sinclair M, Crombie C, Collier DA, Walker N, He L, Clair D (2004) No association between polymorphisms of methylenetetrahydrofolate reductase gene and schizophrenia in both Chinese and Scottish populations. Mol Psychiatry 9:1063–1065

    Article  CAS  PubMed  Google Scholar 

  • Zeisel SH (2009) Importance of methyl donors during reproduction. Am J Clin Nutr 89:673s–677s

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang HY, Luo GA, Liang QL, Wang Y, Yang HH, Wang YM, Zheng XY, Song XM, Chen G, Zhang T, Wu JX (2008) Neural tube defects and disturbed maternal folate- and homocysteine-mediated one-carbon metabolism. Exp Neurol 212:515–521

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, **e B, Du Y, Cheng W, Fang Y, Yu S (2010) Further evidence that methylenetetrahydrofolate reductase A1298C polymorphism is a risk factor for schizophrenia. J Neural Transm 117:1115–1117

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Liu TB, Yang YY, Deng XM, Yan XH, Yang KJ, Rong H (2012) Association between the MTHFR gene polymorphisms and refractory schizophrenia. J Clin Psychiatry 22:293–297 (Chinese)

    CAS  Google Scholar 

  • Zhang Y, Yan H, Tian L, Wang F, Lu T, Wang L, Yan J, Liu Q, Kang L, Ruan Y, Zhang D, Yue W (2013) Association of MTHFR C677T polymorphism with schizophrenia and its effect on episodic memory and gray matter density in patients. Behav Brain Res 243:146–152

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhao GQ, Jiao ZA, Wang SM, Liu ZX, Shi H (2008) Association between the 5,10-methylenetetrahydrofolate reductase gene polymorphisms and plasma homocysteine levels in bipolar disorder. J Psychiatry 21:130–132 (Chinese)

    Google Scholar 

  • Zintzaras E (2006) C677T and A1298C methylenetetrahydrofolate reductase gene polymorphisms in schizophrenia, bipolar disorder and depression: a meta-analysis of genetic association studies. Psychiatr Genet 16:105–115

    Article  PubMed  Google Scholar 

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Acknowledgments

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

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Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan road, Hefei, 230032, Anhui, China

    Cai-Yun Hu, Zhen-Zhong Qian, Feng-Feng Gong, Shan-Shan Lu, Fang Feng, Yi-Le Wu, Hui-Yun Yang & Ye-Huan Sun

  2. Centre for Evidence-Based Practice, Anhui Medical University, No. 81 Meishan road, Hefei, 230032, Anhui, China

    Ye-Huan Sun

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  1. Cai-Yun Hu
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Correspondence to Ye-Huan Sun.

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C.-Y. Hu and Z.-Z. Qian contributed equally to this work

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Hu, CY., Qian, ZZ., Gong, FF. et al. Methylenetetrahydrofolate reductase (MTHFR) polymorphism susceptibility to schizophrenia and bipolar disorder: an updated meta-analysis. J Neural Transm 122, 307–320 (2015). https://doi.org/10.1007/s00702-014-1261-8

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