Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism: evidence of genetic susceptibility

Metabolic Brain Disease

Volumn 31, Issue 4, 2016, Pages 727-735

  Rai, Vandana ^a  

^a VEER BAHADUR SINGH PURVANCHAL UNIVERSITY   (India)

Author keywords

Autism; C677T polymorphism; Homocysteine; Meta analysis; Methylation; MTHFR

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2);

ALLELE; ASIAN; AUTISM; CAUCASIAN; CONTROL; GENE EXPRESSION; GENETIC ASSOCIATION; GENETIC MODEL; GENETIC POLYMORPHISM; GENETIC SUSCEPTIBILITY; GENOTYPE; HUMAN; PATHOGENESIS; REVIEW; SENSITIVITY ANALYSIS; GENETIC PREDISPOSITION; GENETICS; META ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM;

ALLELES; AUTISTIC DISORDER; GENETIC PREDISPOSITION TO DISEASE; HUMANS; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84960081897     PISSN: 08857490     EISSN: 15737365     Source Type: Journal    
DOI: 10.1007/s11011-016-9815-0     Document Type: Review

References (65)

1. Ali A, Waly MI, Al-Farsi YM, Essa MM, Al-Sharbati MM, Deth RC (2011) Hyperhomocysteinemia among Omani autistic children: A case-control study. Acta Biochim Pol 58:547–551
2. Almeida OP, Flicker L, Lautenschlager NT, Leedman P, Vasikaran S, Van Bock-Xmeer FM (2005) Contribution of the MTHFR gene to the causal pathway for depression, anxiety and cognitive impairment in later life. Neurobiol Aging 26:251–257
3. Anagnostou E, Taylor MJ (2011) Review of neuroimaging in autism spectrum disorders: what have we learned and where we go from here. Mol Autism 2:4–13
4. Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M (1995) Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 25:63–77
5. Barbato JC, Catanescu O, Murray K, DiBello PM, Jacobsen DW (2007) Targeting of metallothioneine by L-homocysteine: a novel mechanism for disruption of zinc and redox homeostasis. Arterioscler Thromb Vasc Biol 27:49–54
6. Bax L, Yu LM, Ikeda N, Tsuruta H, Moons KG (2006) Development and validation of MIX: comprehensive free software for meta-analysis of causal research data. BMC Med Res Methodol 6:50
7. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101
8. Boris M, Goldblatt A, Galanko J, James J (2004) Association of MTHFR gene variants with autism. J Am Phys Surg 9:106–108
9. Botto LD, Yang Q (2000) 5, 10-methylenetetrahydrofolate reductase variants and congenital anomalies: A huge review. Am J Epidemiol 151:862–877
10. Centers for Disease Control and Prevention (2012) Prevalence of autism spectrum disorders—autism and developmental disabilities monitoring network, 14 sites, United States, 2008. MMWR Surveill Summ 61:1–19
11. Christensen B, Frosst P, Lussier-Cacan S, Selhub J, Goyette P, Rosenblatt DS, Gravel RA, Forbes P, Rozen R (1997) Correlation of a common mutation in the methylenetetrahydrofolate reductase gene with plasma homocysteine in patients with premature coronary artery disease. Arterioscler Thromb Vasc Biol 17:569–573
12. Courchesne E, Pierce K, Schumann CM, Redcay E, Buckwalter JA, Kennedy DP, Morgan J (2007) Mapping early brain development in autism. Neuron 56:399–413
13. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188
14. Devlin AM, Clarke R, Birks J, Evans JG, Halsted CH (2006) Interactions among polymorphisms in folate-metabolizing genes and serum total homocysteine concentrations in a healthy elderly population. Am J Clin Nutr 83:708–713
15. Divyakolu S, Tejaswini Y, Thomas W, Thumoju S, Sreekanth VR, Vasavi M, OmSai VR, Nagaratna V, Hasan Q, Ahuja YR (2013) Evaluation of C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in various neurological disorders. Neurol Disord 2:142–146
16. dos Santos PA, Longo D, Brandalize AP, Schüler-Faccini L (2010) MTHFR C677T is not a risk factor for autism spectrum disorders in South Brazil. Psychiatr Genet 20:187–189
17. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. British Med J 315:629–634
18. Flickera L, Martins RN, Thomas J, Acres J, Taddei K, Norman P, Jamrozik K, Almeida OP (2004) Homocysteine, Alzheimer genes and proteins, and measures of cognition and depression in older men. J Alzheimer’s Dis 6:329–336
19. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Mathews RG, Boers GJH, den Heijer M, Kluijtmans LAJ, 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
20. Frustaci A, Neri M, Cesario A, Adams JB, Domenici E, Bernardina BD, et al. (2012) Oxidative stress-related biomarkers in autism: systematic review and meta-analysis. Free Rad Med 52(10):2128–2141
21. Fumagalli F, Racagni G, Colombo E, Riva MA (2003) BDNF gene expression is reduced in the frontal cortex of dopamine transporter knockout mice. Mol Psychiatr 8(11):898–899
22. Gao XH, Zhang GY, Wang Y, Zhang HY (2014) Correlations of MTHFR 677C.T polymorphism with cardiovascular disease in patients with end-stage renal disease: a meta-analysis. PLoS one 9(7):e102323
23. Guo T, Chen H, Liu B, Ji W, Yang C (2012) Methylenetetrahydrofolate reductase polymorphisms C677T and risk of autism in the Chinese Han population. Genet Test Mole Biomark 16:968–973
24. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558
25. Hu CY, Qian ZZ, Gong FF, Lu SS, Feng F, Wu YL, Yang HY, Sun YH (2014) Methylenetetrahydrofolate reductase (MTHFR) polymorphism susceptibility to schizophrenia and bipolar disorder: an updated meta-analysis. J Neural Transm 122(2):307–320
26. Ignarro LJ, Shideman FE (1968) Catechol-O-methyl transferase and monoamine oxidase activities in the heart and liver of the embryonic and developing chick. J Pharmacol Exp Ther 159(1):29–37
27. James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA (2004) Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr 80:1611–1617
28. James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong DH, Cutler P, Bock K, Boris M, Bradstreet JJ, Baker SM, Gaylor DW (2006) Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med genet. part B. Neuropsychiat Genet 141B:947–956
29. Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826
30. Li E (2002) Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet 3:662–673
31. Liu X, Solehdin F, Cohen IL, Gonzalez MG, Jenkins EC, Lewis MES, Holden JA (2011) Population- and family-based studies associate the MTHFR gene with idiopathic autism in simplex families. J Autism Develop Dis 41:938–944
32. Main PAE, Angley MT, Thomas P, O’Doherty CE, Fenech M (2010) Folate and methionine metabolism in autism: a systematic review. Am J Clin Nutr 91:1598–1620
33. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748
34. Meguid N, Khalil R, Gebril O, El-Fishawy P (2015) Evaluation of MTHFR genetic polymorphism as a risk factor in Egyptian Autistic Children and Mothers. J Psychiatry 18:1. doi:10.4172/Psychiatry.1000179
35. Melnyk S, Fuchs GJ, Schulz E, Lopez M, Kahler SG, Fussell JJ, et al. (2011) Metabolic imbalance associated with methylation dysregulation and oxidative damage in children with autism. J Autism Dev Disord 42:367–377
36. Miller AL (2003) The methionine-homocysteine cycle and its effects on cognitive diseases. Altern Med Rev 8:7–19
37. Mohammad NS, Jain JM, Chintakindi KP, Singh RP, Naik U, Akella RR (2009) Aberrations in folate metabolic pathway and altered susceptibility to autism. Psychiat Genet 19:171–176
38. Munafo MR, Flint J (2004) Meta-analysis of genetic association studies. Trends Genet 20:439–444
39. Park JW, Ro MJ, Pyun JA, Kwack KB, Nam M, Bang HJ, Yang JW, Choi KS, Kim SK, Chung JH (2014) MTHFR 1298 A > C is a risk factor for autism spectrum disorder in the Korean population. Psychiat Res 215:258–259
40. Pasca SP, Dronca E, Kaucsar T, Craciun EC, Endreffy E, Ferencz BK, Iftene F, Benga I, Cornean R, Banerjee R, Dronca M (2009) One carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders. J Cell Mole Med 13:4229–4238
41. Peerbooms OL, van Os J, Drukker M, Kenis G, Hoogveld L (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(8):1530–1543
42. Pepe G, Venegas OC, Giusti B, Brunelli T, Marcucci R, Attanasio M, Rickards O, De Stefano GF, Prisco D, Gensini GF, Abbate R (1998) Heterogeneity in world distribution of thermolabile C677T mutation in 5,10-methylenetetrahydrofolate reductase. Am J Hum Genet 63:917–920
43. Pu D, Shen Y, Wu J (2013) Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis. Autism Res 6(5):384–392
44. Rai V (2011) Evaluation of methylenetetrahydrofolate reductase gene variant (C677T) as risk factor for bipolar disorder. Cell Mol Biol 57:OL1558–OL1566
45. Rai V (2014a) Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene and susceptibility to depression in Asian population: a systematic meta-analysis. Cell Mol Biol 60(3):29–36
46. Rai V (2014b) The methylenetetrahydrofolate reductase C677T polymorphism and breast cancer risk in Asian populations. Asian Pac J Cancer Prev 15:5853–5860
47. Rai V, Yadav U, Kumar P (2012) Prevalence of methylenetetrahydrofolate reductase C677T polymorphism in Eastern Uttar Pradesh. Ind J Hum Genet 18:43–46
48. Rai V, Yadav U, Kumar P, Yadav SK, Mishra OP (2014) Maternal methylenetetrahydrofolate reductase C677T polymorphism and down syndrome risk: a meta-analysis from 34 studies. PLoS one 9:e108552
49. Ryan BM, Weir DG (2001) Relevance of folate metabolism in the pathogenesis of colorectal cancer. J Lab Clin Med 138:164–176
50. Schaevitz LR, Berger-Sweeney JE (2012) Gene–environment interactions and epigenetic pathways in autism: the importance of one-carbon metabolism. ILAR J 53(3–4):322–340
51. Schatz RA, Wilens TE, Sellinger OZ (1981) Decreased transmethylation of biogenic amines after in vivo elevation of brain S-adenosyl-l-homocysteine. J Neurochem 36(5):1739–1748
52. Schendel DE, Overgaard M, Christensen J, Hjort L, Jørgensen M, Vestergaard M, Parner ET (2016) Association of psychiatric and neurologic comorbidity with mortality among persons with autism Spectrum disorder in a Danish population. JAMA Pediatr. doi:10.1001/jamapediatrics.2015.3935
53. Schmidt RJ, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tancredi DJ, Tassone F, Hertz-Picciotto I (2011) Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism. Epidemiol 22:476–485
54. Selhub J, Rosenberg IH (1996) Folic acid. In: Ziegler EE, filer LJ Jr, present knowledge in nutrition, 7th edn. International Life Sciences Institute Press, Washington, DC, pp. 206–219
55. Sener EF, Oztop DB, Usuf Ozkul Y (2014) MTHFR gene C677T polymorphism in Autism Spectrum Disorders. Genet Res Int 2014:Article ID 698574
56. Shawky RM, El-baz F, Kamal TM, Elhossiny RM, Ahmed MA, El Nady GH (2014) Study of genotype–phenotype correlation of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in a sample of Egyptian autistic children. Egypt J Med Hum Gene 15:335–341
57. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA 283(15):2008–2012
58. Suh JH, Walsh WJ, McGinnis WR, Lewis A, Ames BN (2008) Altered sulfur amino acid metabolism in immune cells of children diagnosed with autism. Am J Biochem Biotech 4:105–113
59. Tu MC, Huang CW, Chen NC, Chang WN, Lui CC, Chen CF, et al. (2010) Hyperhomocysteinemia in Alzheimer dementia patients and cognitive decline after 6 months follow-up period. Acta Neurol Taiwan 19:168–177
60. Wass S (2011) Distortions and disconnections: disrupted brain connectivity in autism. Brain Cogn 75(1):18–28
61. Whitehead A (2002) Meta-Analysis of controlled clinical trials. Chichester, West Sussex, England, John Wiley & Sons Ltd
62. Yadav U, Kumar P, Yadav SK, Mishra OP, Rai V (2015) Polymorphisms in folate metabolism genes as maternal risk factor for neural tube defects: an updated meta-analysis. Meta Brain Dis 30:7–24
63. Zhang MY, Miaoa L, Li YS, Hub GY (2010) Meta-analysis of the methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to Alzheimer’s disease. Neurosci Res 68:142–150
64. Zhang P, Gao X, Zhang Y, Hu Y, Ma H, Wang W, et al. (2014) Association between MTHFR C677T polymorphism and venous thromboembolism risk in the Chinese population: A meta-analysis of 24 case-control studies. Angiology 66(5):422–432
65. Zhao M, Ren Y, Shen L, Zhang Y, Zhou B (2014) Association between MTHFR C677T and A1298C polymorphisms and NSCL/P risk in Asians: a meta- analysis. PLoS one 9:e88242