Skip to main content

Advertisement

SpringerLink
Log in

Distribution of MTHFR C677T Gene Polymorphism in Healthy North Indian Population and an Updated Meta-analysis

  • Original Article
  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate pathway. Several polymorphisms were reported in MTHFR gene but C677T polymorphism is most studied and it has been reported to be risk factor for several diseases/disorders. The present study was designed to explore the frequency of MTHFR C677T polymorphism in North Indian healthy population. In addition to this a meta-analysis of published articles was also performed to estimate the global prevalence of MTHFR C677T polymorphism. A total of 1000 unrelated healthy subjects were selected for MTHFR C677T polymorphism analysis. Different databases were searched for eligible articles. Prevalence proportion with 95 % CI was used to determine global prevalence of T allele and TT genotype. Meta-analysis was performed by Open meta-analyst. In 1000 blood samples analyzed, the frequency of T allele and TT genotype was 11 and 1 % respectively. Results of the meta-analysis showed that the global prevalence of T allele and TT genotype were 24.0 % (95 % CI 21.7–26.5) and 7.7 % (95 % CI 6.5–8.9) respectively. In sub-group meta-analysis, the lowest frequency of T allele was found in Africans (10.3 %; 95 % CI 3.8–16.8), and highest in Europeans (34.1 %; 95 % CI 31.9–36.3). The frequency of T allele in the North India is 11 %. The results of the meta-analysis showed that the frequency of the T allele and the TT genotype of C677T is highest in the Caucasian population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Goyette P, Pai A, Milos R, Frosst P, Tran P, Chen Z, et al. Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR). Mamm Genome. 1998;9:652–6.

    Article  CAS  PubMed  Google Scholar 

  2. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111–3.

    Article  CAS  PubMed  Google Scholar 

  3. Rozen R. Genetic predisposition to hyperhomocysteinemia: deficiency of methylenetetrahydrofolate reductase (MTHFR). Thromb Haemost. 1997;78:523–6.

    CAS  PubMed  Google Scholar 

  4. Guenther BD, Sheppard CA, Tran P, Rozen R, Matthews RG, Ludwig ML. The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia. Nat Struct Biol. 1999;6:359–65.

    Article  CAS  PubMed  Google Scholar 

  5. Yamada K, Chen Z, Rozen R, Matthews RG. Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. Proc Natl Acad Sci USA. 2001;98:14853–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pejchal R, Campbell E, Guenther BD, Lennon BW, Matthews RG, Ludwig ML. Structural perturbations in the Ala → Val polymorphism of methylenetetrahydrofolate reductase: how binding of folates may protect against inactivation. Biochemistry. 2006;45:4808–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yadav U, Kumar P, Rai V. Docking study of MTHFR with FAD by Hex. J Comput Intell Bioinform. 2011;4(1):171–8.

    Google Scholar 

  8. Homberger A, Linnebank M, Winter C, Willenbring H, Marquardt T, Harms E, et al. Genomic structure and transcript variants of the human methylenetetrahydrofolate reductase gene. Eur J Hum Genet. 2000;8(9):725–9.

    Article  CAS  PubMed  Google Scholar 

  9. Hobbs CA, Sherman SL, Yi P, Hopkins SE, Torfs CP, Hine RJ, et al. Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome. Am J Hum Genet. 2000;67:623–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cyril C, Rai P, Chandra N, Gopinath PM, Satyamoorthy K. MTHFR gene variants C677T, A1298C and association with Down syndrome: a case-control study from South India. Indian J Hum Genet. 2009;15:60–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Godbole K, Gayathri P, Ghule S, Sasirekha BV, Kanitkar-Damle A, Memane N, et al. Maternal one-carbon metabolism, MTHFR and TCN2 genotypes and neural tube defects in India. Birth Defects Res A Clin Mol Teratol. 2011;91(9):848–56.

    Article  CAS  PubMed  Google Scholar 

  12. Mills JL, Molloy AM, Parle-McDermott A, Troendle JF, Brody LC, Conley MR, et al. Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate. Birth Defects Res A Clin Mol Teratol. 2008;82(9):636–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Benes P, Kanková K, Muzík J, Groch L, Benedik J. Methylenetetrahydrofolate reductase polymorphism, type II diabetes mellitus, coronary artery disease, and essential hypertension in the Czech population. Mol Genet Metab. 2007;73:188–95.

    Article  Google Scholar 

  14. Lakshmi SV, Naushad SM, Ruparsree Y, Rao DS, Kutala VK. Interactions of 5′-UTR thymidylate synthase polymorphism with 677C→T methylene tetrahydrofolate reductase and 66A→G methyltetrahydrofolate homocysteine methyl-transferase reductase polymorphisms determine susceptibility to coronary artery disease. J Atheroscler Thromb. 2010;18:56–64.

    Article  Google Scholar 

  15. Gupta N, Gupta S, Dama M, David A, Khanna G, Khanna A, et al. Strong association of 677 C>T substitution in the MTHFR gene with male infertility-a study on an Indian population and a meta-analysis. PLoS ONE. 2011;6:e22277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jönsson EG, Larsson K, Vares M, Hansen T, Wang AG, Djurovic S, et al. Two methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, schizophrenia and bipolar disorder: an association study. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(6):976–82.

    Article  PubMed  Google Scholar 

  17. Kotsopoulos J, Zhang WW, Zhang S, McCready D, Trudeau M, Zhang P, et al. Polymorphisms in folate metabolizing enzymes and transport proteins and the risk of breast cancer. Breast Cancer Res Treat. 2008;112:585–93.

    Article  CAS  PubMed  Google Scholar 

  18. Bartlett JMS, White A. Extraction of DNA from whole blood. In: Bartlett JMS, Stirling D, editors. Methods in molecular biology, vol. 226: PCR protocols. 2nd ed. Totowa: Humana Press Inc; 2003. p. 29–31.

    Google Scholar 

  19. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719–48.

    CAS  PubMed  Google Scholar 

  20. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  PubMed  Google Scholar 

  21. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Article  PubMed  Google Scholar 

  22. Whitehead A. Meta-analysis of controlled clinical trials. West Sussex: Wiley; 2002.

    Book  Google Scholar 

  23. Wallace BC, Dahabreh IJ, Trikalinos TA, Lau J, Trow P, Schmid CH. Closing the gap between methodologists and end-users: R as a computational back-end. J Stat Softw. 2013;49:1–15.

    Google Scholar 

  24. StatPlanet software. http://www.statsilk.com/software/statplanet.

  25. Schneider JA, Rees DC, Liu YT, Clegg JB. Worldwide distribution of a common methylenetetrahydrofolate reductase mutation. Am J Hum Genet. 1998;62:1258–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wilcken B, Bamforth F, Li Z, Zhu H, Ritvanen A, Renlund M, et al. Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world-wide. J Med Genet. 2003;40:619–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rosenberg N, Murata M, Ikeda Y, Opare-Sem O, Zivelin A, Geffen E, et al. The frequent 5,10-methylenetetrahydrofolate reductase C677T polymorphism is associated with a common haplotype in whites, Japanese, and Africans. Am J Hum Genet. 2002;70:758–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ameen G, Irani-Hakime N, Fawaz NA, Mahjoub T, Almawi WY. An Arab selective gradient in the distribution of factor V G1691A (Leiden), prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T. J Thromb Haemost. 2005;3:2126–7.

    Article  CAS  PubMed  Google Scholar 

  29. Arruda VR, Siqueira LH, Goncalves MS, von Zuben PM, Soares MC, Menezes R, et al. Prevalence of the mutation C677→T in the methylene tetrahydrofolate reductase gene among distinct ethnic groups in Brazil. Am J Med Genet. 1998;78:332–5.

    Article  CAS  PubMed  Google Scholar 

  30. Franco RF, Araújo AG, Guerreiro JF, Elion J, Zago MA. Analysis of the 677 C→T mutation of the methylenetetrahydrofolate reductase gene in different ethnic groups. Thromb Haemost. 1998;79(1):119–21.

    CAS  PubMed  Google Scholar 

  31. Barbosa PR, Stabler SP, Machado AL, Braga RC, Hirata RD, Hirata MH, et al. Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women. Eur J Clin Nutr. 2008;62:1010–21.

    Article  CAS  PubMed  Google Scholar 

  32. Stur E, Silveira AN, Selvatici LS, Alves LN, de Vargas Wolfgramm E, Tovar TT, et al. Polymorphism analysis of MTHFR, factor II, and factor V genes in the Pomeranian population of Espirito Santo, Brazil. Genet Test Mol Biomarkers. 2012;16:219–22.

    Article  CAS  PubMed  Google Scholar 

  33. Romero-Sánchez C, Gómez-Gutierrez A, Gómez PE, Casas-Gomez MC, Briceño I. C677T (rs1801133) MTHFR gene polymorphism frequency in a Colombian population. Colomb Med (Cali). 2015;46(2):75–9.

    Google Scholar 

  34. Mack R, Chowdary D, Streck D, Dermody J. Inherited thrombophilia genes in minorities. Genet Test. 1999;3:371–3.

    Article  CAS  PubMed  Google Scholar 

  35. Stevenson RE, Schwartz CE, Du YZ, Adams MJ Jr. Differences in methylenetetrahydrofolate reductase genotype frequencies, between Whites and Blacks. Am J Hum Genet. 1997;60:229–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Mutchinick OM, Lopez MA, Luna L, Waxman J, Babinsky VE. High prevalence of the thermolabile methylenetetrahydrofolate reductase variant in Mexico: a country with a very high prevalence of neural tube defects. Mol Genet Metab. 1999;68:461–7.

    Article  CAS  PubMed  Google Scholar 

  37. Rady PL, Szucs S, Grady J, Hudnall SD, Kellner LH, Nitowsky H, et al. Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) in ethnic populations in Texas; a report of a novel MTHFR polymorphic site, G1793A. Am J Med Genet. 2002;107:162–8.

    Article  PubMed  Google Scholar 

  38. Bailey LB, Duhaney RL, Maneval DR, Kauwell GP, Quinlivan EP, Davis SR, et al. Vitamin B-12 status is inversely associated with plasma homocysteine in young women with C677T and/or A1298C methylenetetrahydrofolate reductase polymorphisms. J Nutr. 2002;132(7):1872–8.

    CAS  PubMed  Google Scholar 

  39. Chowdary D, Streck D, Schwalb MN, Dermody JJ. High incidence of two methylenetetrahydrofolate reductase mutations (C677T and A1298C) in Hispanics. Genet Test. 2003;7:255–7.

    Article  CAS  PubMed  Google Scholar 

  40. Esfahani ST, Cogger EA, Caudill MA. Heterogeneity in the prevalence of methylenetetrahydrofolate reductase gene polymorphisms in women of different ethnic groups. J Am Diet Assoc. 2003;103:200–7.

    Article  PubMed  Google Scholar 

  41. Vaughn JD, Bailey LB, Shelnutt KP, Dunwoody KM, Maneval DR, Davis SR, et al. Methionine synthase reductase 66A→G polymorphism is associated with increased plasma homocysteine concentration when combined with the homozygous methylenetetrahydrofolate reductase 677C→T variant. J Nutr. 2004;134:2985–90.

    CAS  PubMed  Google Scholar 

  42. Tsai MY, Loria CM, Cao J, Kim Y, Siscovick DS, Schreiner PJ, et al. Polygenic association with total homocysteine in the post-folic acid fortification era: the CARDIA study. Mol Genet Metab. 2009;98:181–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ramos MA, Mares RE, Avalos ED, Hernandez A, Hernandez R, Lameda R, et al. Pharmacogenetic screening of N-acetyltransferase 2, thiopurine s-methyltransferase, and 5,10-methylene-tetrahydrofolate reductase polymorphisms in Northwestern Mexicans. Genet Test Mol Biomarkers. 2011;15:351–5.

    Article  CAS  PubMed  Google Scholar 

  44. Harmon DL, Woodside JV, Yarnell JW, McMaster D, Young IS, McCrum EE, et al. The common ‘thermolabile’ variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia. QJM. 1996;89:571–7.

    Article  CAS  PubMed  Google Scholar 

  45. Bowen DJ, Bowley S, John M, Collins PW. Factor V Leiden (G1691A), the prothrombin 3′-untranslated region variant (G20210A) and thermolabile methylenetetrahydrofolate reductase (C677T): a single genetic test genotypes all three loci-determination of frequencies in the S. Wales population of the UK. Thromb Haemost. 1998;79:949–54.

    CAS  PubMed  Google Scholar 

  46. Hill AE, FitzPatrick DR. MS-PCR assay to detect 677C→T mutation in the 5,10-methylenetetrahydrofolate reductase gene. J Inherit Metab Dis. 1998;21:694–5.

    Article  CAS  PubMed  Google Scholar 

  47. Antoniadi T, Hatzis T, Kroupis C, Economou-Petersen E, Petersen MB. Prevalence of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in a Greek population of blood donors. Am J Hematol. 1999;61:265–7.

    Article  CAS  PubMed  Google Scholar 

  48. Chango A, Boisson F, Barbe F, Quilliot D, Droesch S, Pfister M, et al. The effect of 677C→T and 1298A→C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects. Br J Nutr. 2000;83:593–6.

    Article  CAS  PubMed  Google Scholar 

  49. Mynett-Johnson LA, Keenan C, Black IL, Livingstone WJ, Lawler M, Roche HM, et al. Thermolabile methylenetetrahydrofolate reductase (C677T): frequency in the Irish population. Ir J Med Sci. 2002;171:37–9.

    Article  CAS  PubMed  Google Scholar 

  50. Zijno A, Andreoli C, Leopardi P, Marcon F, Rossi S, Caiola S, et al. Folate status, metabolic genotype, and biomarkers of genotoxicity in healthy subjects. Carcinogenesis. 2003;24:1097–103.

    Article  CAS  PubMed  Google Scholar 

  51. Lovricevic I, Franjic BD, Tomicic M, Vrkic N, De Syo D, Hudorovic N, et al. 5,10-Methylenetetrahydrofolate reductase (MTHFR) 677 C→T genetic polymorphism in 228 Croatian volunteers. Coll Antropol. 2004;28:647–54.

    CAS  PubMed  Google Scholar 

  52. Spiridonova MG, Stepanov VA, Maksimova NR, Puzyrev VP. Population study of frequency of methylenetetrahydrofolate reductase C677T gene polymorphism in Yakutia. Genetika. 2004;40:704–8.

    CAS  PubMed  Google Scholar 

  53. Sazci A, Ergul E, Kaya G, Kara I. Genotype and allele frequencies of the polymorphic methylenetetrahydrofolate reductase gene in Turkey. Cell Biochem Funct. 2005;23:51–4.

    Article  CAS  PubMed  Google Scholar 

  54. Parle-McDermott A, Mills JL, Molloy AM, Carroll N, Kirke PN, Cox C, et al. The MTHFR 1298CC and 677TT genotypes have opposite associations with red cell folate levels. Mol Genet Metab. 2006;88:290–4.

    Article  CAS  PubMed  Google Scholar 

  55. Gialeraki A, Politou M, Rallidis L, Merkouri E, Markatos C, Kremastinos D, et al. Prevalence of prothrombotic polymorphisms in Greece. Genet Test. 2008;12:541–7.

    Article  CAS  PubMed  Google Scholar 

  56. Ozarda Y, Sucu DK, Hizli B, Aslan D. Rate of T alleles and TT genotype at MTHFR 677C→T locus or C alleles and CC genotype at MTHFR 1298A→C locus among healthy subjects in Turkey: impact on homocysteine and folic acid status and reference intervals. Cell Biochem Funct. 2009;27:568–77.

    Article  CAS  PubMed  Google Scholar 

  57. Zappacosta B, Romano L, Persichilli S, Cutrone LA, Graziano M, Vittani A, et al. Genotype prevalence and allele frequencies of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in Italian newborns. Labmed. 2009;40(12):732–6.

    Google Scholar 

  58. Gra O, Mityaeva O, Berdichevets I, Kozhekbaeva Z, Fesenko D, Kurbatova O, et al. Microarray-based detection of CYP1A1, CYP2C9, CYP2C19, CYP2D6, GSTT1, GSTM1, MTHFR, MTRR, NQO1, NAT2, HLA-DQA1, and ABO allele frequencies in native Russians. Genet Test Mol Biomarkers. 2010;14:329–42.

    Article  CAS  PubMed  Google Scholar 

  59. Amela K, Rifet T, Zoran J, Jasminka MM. The frequency of C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism in Southern East Bosnian population. J Biomet Biostat. 2013;4:169.

    Article  Google Scholar 

  60. Seremak-Mrozikiewicz A, Barlik M, Borowczak P, Kurzawinska G, Krasnik W, Nowocien G, et al. The frequency of 677C→T polymorphism of MTHFR gene in the Polish population. Arch Perinat Med. 2013;19(1):12–8.

    Google Scholar 

  61. Friedman G, Goldschmidt N, Friedlander Y, Ben-Yehuda A, Selhub J, Babaey S, et al. A common mutation A1298C in human methylenetetrahydrofolate reductase gene: association with plasma total homocysteine and folate concentrations. J Nutr. 1999;129:1656–61.

    CAS  PubMed  Google Scholar 

  62. Zuo M, Lee MJ, Kim MH, Wu Y, Ayaki H, Nishio H, et al. C677T mutation of the methylenetetrahydrofolate reductase gene among the Korean infants in Seoul city. Kobe J Med Sci. 1999;45:271–9.

    CAS  PubMed  Google Scholar 

  63. Pollak RD, Friedlander Y, Pollak A, Idelson M, Bejarano Achache I, Blumenfeld A. Ethnic differences in the frequency of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in healthy Israeli populations. Genet Test. 2000;4:309–11.

    Article  CAS  PubMed  Google Scholar 

  64. Yu J, Chen B, Zhang G, Fu S, Li P. The 677 C→T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in five Chinese ethnic groups. Hum Hered. 2000;50:268–70.

    Article  CAS  PubMed  Google Scholar 

  65. Murakami S, Matsubara N, Saitoh M, Miyakaw S, Shoji M, Kubo T. The relation between plasma homocysteine concentration and methylenetetrahydrofolate reductase gene polymorphism in pregnant women. J Obstet Gynaecol Res. 2001;27:349–52.

    Article  CAS  PubMed  Google Scholar 

  66. Sadewa AH, Sunarti Sutomo R, Hayashi C, Lee MJ, Ayaki H, et al. The C677T mutation in the methylenetetrahydrofolate reductase gene among the Indonesian Javanese population. Kobe J Med Sci. 2002;48:137–44.

    CAS  PubMed  Google Scholar 

  67. Al-Habboubi H, Tamim H, Ameen G, Almawi WY. A common mutation in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene in two Arab communities. J Thromb Haemost. 2003;1:2246–8.

    Article  CAS  PubMed  Google Scholar 

  68. Almawi WY, Ameen G, Tamim H, Finan RR, Irani-Hakime N. Factor V G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677T gene polymorphism in angiographically documented coronary artery disease. J Thromb Thrombolysis. 2004;17:199–205.

    Article  CAS  PubMed  Google Scholar 

  69. Angeline T, Jeyaraj N, Granito S, Tsongalis GJ. Prevalence of MTHFR gene polymorphisms (C677T and A1298C) among Tamilians. Exp Mol Pathol. 2004;77:85–8.

    Article  CAS  PubMed  Google Scholar 

  70. Golbahar J, Fathi Z, Tamadon M. Distribution of 5,10-methylenetetrahydrofolate reductase (C667T) polymorphism and its association with red blood cell 5-methyltetrahydrofolate in the healthy Iranians. Clin Nutr. 2005;24:83–7.

    Article  CAS  PubMed  Google Scholar 

  71. Bhat TA, Mir MR, Qasim I, Misra SS, Kirmani MA. Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase C677T in Kashmiri population. Biotechnology. 2008;7:822–5.

    Article  CAS  Google Scholar 

  72. Sabbagh AS, Mahfoud Z, Taher A, Zaatari G, Daher R, Mahfouz RA. High prevalence of MTHFR gene A1298C polymorphism in Lebanon. Genet Test. 2008;12:75–80.

    Article  CAS  PubMed  Google Scholar 

  73. Saraswathy KN, Mukhopadhyay R, Sinha E, Aggarwal S, Sachdeva MP, Kalla AK. MTHFR C677T polymorphisms among the Ahirs and Jats of Haryana (India). Am J Hum Biol. 2008;20:116–7.

    Article  CAS  PubMed  Google Scholar 

  74. Al-Allawi NA, Avo AS, Jubrael JM. Methylenetetrahydrofolate reductase C677T polymorphism in Iraqi patients with ischemic stroke. Neurol India. 2009;57:631–5.

    Article  PubMed  Google Scholar 

  75. Algasham A, Ismail H, Dewaidar M, Settin AA. Methylenetetrahydrofolate reductase and angiotensin-converting enzyme gene polymorphisms among Saudi population from Qassim region. Genet Test Mol Biomarkers. 2009;13:817–20.

    Article  CAS  PubMed  Google Scholar 

  76. Mansoor A, Mazhar K, Ali L, Muazzam AG, Siddiqi S, Usman S. Prevalence of the C677T single-nucleotide polymorphism in the methylenetetrahydrofolate reductase gene among Pakistani ethnic groups. Genet Test Mol Biomarkers. 2009;13:521–6.

    Article  CAS  PubMed  Google Scholar 

  77. Bagheri M, Abdi Rad I. Frequency of the Methylenetetrahydrofolate reductase 677CT and 1298AC mutations in an Iranian Turkish female population. Maedica (Buchar). 2010;5:171–7.

    Google Scholar 

  78. Misra UK, Kalita J, Srivastava AK, Agarwal S. MTHFR gene polymorphism and its relationship with plasma homocysteine and folate in a North Indian population. Biochem Genet. 2010;48:229–35.

    Article  CAS  PubMed  Google Scholar 

  79. Ghodke Y, Chopra A, Shintre P, Puranik A, Joshi K, Patwardhan B. Profiling single nucleotide polymorphisms (SNPs) across intracellular folate metabolic pathway in healthy Indians. Indian J Med Res. 2011;133:274–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Murry B, Vakha N, Achoubi N, Sachdeva MP, Saraswathy KN. APOE, MTHFR, LDLR and ACE polymorphisms among Angami and Lotha Naga populations of Nagaland, India. J Community Health. 2011;36:975–85.

    Article  PubMed  Google Scholar 

  81. Sukla KK, Raman R. Association of MTHFR and RFC1 gene polymorphism with hyperhomocysteinemia and its modulation by vitamin B12 and folic acid in an Indian population. Eur J Clin Nutr. 2012;66:111–8.

    Article  CAS  PubMed  Google Scholar 

  82. Sachdeva S, Saraswathy KN, Gulabani M, Kaushik S, Sachdeva MP, Puri M, et al. MTHFR C677T polymorphism among three Mendelian populations: a study from North India. Biochem Genet. 2012;50:893–7.

    Article  CAS  PubMed  Google Scholar 

  83. Saraswathy KN, Asghar M, Samtani R, Murry B, Mondal PR, Ghosh PK, et al. Spectrum of MTHFR gene SNPs C677T and A1298C: a study among 23 population groups of India. Mol Biol Rep. 2012;39:5025–31.

    Article  CAS  PubMed  Google Scholar 

  84. Dajani R, Fathallah R, Arafat A, AbdulQader ME, Hakooz N, Al-Motassem Y, et al. Prevalence of MTHFR C677T single nucleotide polymorphism in genetically isolated populations in Jordan. Biochem Genet. 2013;51:780–8.

    Article  CAS  PubMed  Google Scholar 

  85. Yang B, Liu Y, Li Y, Fan S, Zhi X, Lu X, et al. Geographical distribution of MTHFR C677T, A1298C and MTRR A66G gene polymorphisms in China: findings from 15357 adults of Han nationality. PLoS ONE. 2013;8:e57917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Wu X, Wang X, Chan Y, Jia S, Luo Y, Tang W. Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for down syndrome offspring: a meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2013;167(2):154–9.

    Article  CAS  PubMed  Google Scholar 

  87. Rai V, Yadav U, Kumar P, Yadav SK, Mishra OP. Maternal methylenetetrahydrofolate reductase C677T polymorphism and Down syndrome risk: a meta-analysis from 34 studies. PLoS ONE. 2014;9:e108552.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Verkleij-Hagoort A, Bliek J, Sayed-Tabatabaei F, Ursem N, Steegers E, Steegers-Theunissen R. Hyperhomocysteinemia and MTHFR polymorphisms in association with orofacial clefts and congenital heart defects: a meta-analysis. Am J Med Genet A. 2007;143A:952–60.

    Article  CAS  PubMed  Google Scholar 

  89. Xuan C, Bai XY, Gao G, Yang Q, He GW. Association between polymorphism of methylenetetrahydrofolate reductase (MTHFR) C677T and risk of myocardial infarction: a meta-analysis for 8,140 cases and 10,522 controls. Arch Med Res. 2011;42:677–85.

    Article  CAS  PubMed  Google Scholar 

  90. Yang S, Zhang J, Feng C, Huang G. MTHFR 677T variant contributes to diabetic nephropathy risk in Caucasian individuals with type 2 diabetes: a meta-analysis. Metabolism. 2013;62(4):586–94.

    Article  CAS  PubMed  Google Scholar 

  91. Peerbooms OL, van Os J, Drukker M, Kenis G, Hoogveld L, MTHFR in Psychiatry Group, et al. Meta-analysis of MTHFR gene variants in schizophrenia, bipolar disorder and unipolar depressive disorder: evidence for a common genetic vulnerability? Brain Behav Immun. 2011;25(8):1530–43.

    Article  CAS  PubMed  Google Scholar 

  92. Yadav U, Kumar P, Yadav SK, Mishra OP, Rai V. Polymorphisms in folate metabolism genes as maternal risk factor for neural tube defects: an updated meta-analysis. Metab Brain Dis. 2015;30:7–24.

    Article  CAS  PubMed  Google Scholar 

  93. Rai V. The methylenetetrahydrofolate reductase C677T polymorphism and breast cancer risk in Asian populations. Asian Pac J Cancer Prev. 2014;15(14):5853–60.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to all subjects for their participation in the study. This study was supported by the financial assistance from Department of Biotechnology, New Delhi (No. BT/PR98887/SPD/11/1028/2007) to Vandana Rai to conduct this study.

Author information

Authors and Affiliations

  1. Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, UP, 222 003, India

    Upendra Yadav, Pradeep Kumar & Vandana Rai

  2. Department of Psychiatry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

    Sanjay Gupta

Authors
  1. Upendra Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pradeep Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sanjay Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vandana Rai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vandana Rai.

Ethics declarations

Conflict of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yadav, U., Kumar, P., Gupta, S. et al. Distribution of MTHFR C677T Gene Polymorphism in Healthy North Indian Population and an Updated Meta-analysis. Ind J Clin Biochem 32, 399–410 (2017). https://doi.org/10.1007/s12291-016-0619-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12291-016-0619-0

Keywords

Search

Navigation