Skip to main content
SpringerLink
Log in

MTHFR Polymorphisms Involved in Vitamin B12 Deficiency Associated with Atrophic Gastritis

  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Genetic polymorphisms affecting methylentetrahydrofolate reductase (MTHFR) activity may influence hematological and neurological dysfunction in cobalamin-deficient patients. We studied the prevalence of C677T and A1298C polymorphisms by analyzing genomic DNA in 30 cobalamin-deficient patients. No significant difference was found in 677 and 1298 genotype distribution with respect to hematological parameters, B12 and folate levels, and neurological symptoms. The two MTHFR polymorphisms were not protective against anemia or neurological dysfunction in patients with cobalamin deficiency; however, we found evidence of a significant increase in atrophic gastritis in the 677TT group (P = 0.009) but not for the 1298CC genotype. Based on observations that inadequate cobalamin intake and reduced MTHFR activity might be significant risk factors for gastric cancer, and the increased risk of gastric cancer shown in patients affected by atrophic gastritis, we speculate that concomitant atrophic gastritis and impaired MTHFR function could have a role in the development of gastric cancer.

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

Similar content being viewed by others

References

  • Boccia S, Hung R, Ricciardi G, Gianfagna F, Ebert MP, Fang JY, Gao CM, Götze T, Graziano F, Lacasaña-Navarro M, Lin D, López-Carrillo L, Qiao YL, Shen H, Stolzenberg-Solomon R, Takezaki T, Weng YR, Zhang FF, van Duijn CM, Boffetta P, Taioli E (2008) Meta- and pooled analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer risk: a huge-GSEC review. Am J Epidemiol 167(5):505–516

    Article  PubMed  Google Scholar 

  • Carmel R, Pullarkat V (2003) Gene polymorphisms associated with diminished activity of 5,10-methylentetrahydrofolate reductase do not explain the clinical manifestations of cobalamin deficiency. Br J Haematol 120(5):907–909

    Article  PubMed  CAS  Google Scholar 

  • Carmel R, Green R, Rosenblatt DS, Watkins D (2003a) Update on cobalamin, folate, and homocysteine. Hematol Am Soc Hematol Educ Program 1:62–81

    Google Scholar 

  • Carmel R, Melnyk S, James SJ (2003b) Cobalamin deficiency with and without neurologic abnormalities: differences in homocysteine and methionine metabolism. Blood 101(8):3302–3308

    Article  PubMed  CAS  Google Scholar 

  • Castro R, Rivera I, Ravacso P, Camilo ME, Jakobs C, Blom HJ, de Almeida IT (2004) 5,10-methylentetrahydrofolate reductase (MTHFR) 677C-T and 1298A-C mutations are associated with DNA hypomethylation. J Med Genet 41:454–458

    Article  PubMed  CAS  Google Scholar 

  • Chiusolo P, Reddiconto G, Cimino G, Sica S, Fiorini A, Farina G, Vitale A, Sorà F, Laurenti L, Bartolozzi F, Fazi P, Mandelli F, Leone G (2004) Methylenetetrahydrofolate reductase genotypes do not play a role in acute lymphoblastic leukemia pathogenesis in the Italian population. Haematologica 89(2):139–144

    PubMed  CAS  Google Scholar 

  • Correa P (1988) A human model of gastric carcinogenesis. Cancer Res 48:3554–3560

    PubMed  CAS  Google Scholar 

  • Dunn BK (2003) Hypomethylation: one side of a larger picture. Ann N Y Acad Sci 983:28–42

    Article  PubMed  CAS  Google Scholar 

  • Friso S, Choi SW, Girelli D, Mason JB, Dolnikowski GG, Bagley PJ, Olivieri O, Jacques PF, Rosenberg IH, Corrocher R, Selhub J (2002) A common mutation in the 5,10-methylentetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. Proc Natl Acad Sci USA 99:5606–5611

    Article  PubMed  CAS  Google Scholar 

  • Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylentetrahydrofolate reductase. Nat Genet 10(1):111–113

    Article  PubMed  CAS  Google Scholar 

  • Graziano F, Kawakami K, Ruzzo A, Watanabe G, Santini D, Pizzagalli F, Bisonni R, Mari D, Floriani I, Catalano V, Silva R, Tonini G, Torri V, Giustini L, Magnani M (2006) Methylentetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk Italian population. Int J Cancer 18:628–632

    Article  CAS  Google Scholar 

  • Kano Y, Sakamoto S, Hida K, Suda K, Takaku F (1982) 5-methylentetrahydrofolate related enzymes and DNA polymerase α activities in bone marrow cells from patients with vitamin B12 deficient megaloblastic anemia. Blood 59(4):832–837

    PubMed  CAS  Google Scholar 

  • Lahner E, Bordi C, Cattaruzza MS, Iannoni C, Milione M, Delle Fave G, Annibale B (2005) Long-term follow-up in atrophic body gastritis patients: atrophy and intestinal metaplasia are persistent lesions irrespective of Helicobacter pylori infection. Aliment Pharmacol Ther 2:471–481

    Article  Google Scholar 

  • Ohata H, Kitauchii S, Yoshimura N, Mugitani K, Iwane M, Nakamura H, Yoshikawa A, Yanaoka K, Arii K, Tamai H, Shimizu Y, Takeshita T, Mohara O, Ichinose M (2004) Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer. Int J Cancer 109:138–143

    Article  PubMed  CAS  Google Scholar 

  • Smulders YM, Smith DE, Kok RM, Teerlink T, Swinkels DW, Stehouwer CD, Jakobs C (2006) Cellular folate vitamer distribution during and after correction of vitamin B12 deficiency: a case of the methylfolate trap. Br J Haematol 132(5):623–629

    Article  PubMed  CAS  Google Scholar 

  • Vollset SE, Igland J, Jenab M, Fredriksen A, Meyer K, Eussen S, Gjessing HK, Ueland PM, Pera G, Sala N, Agudo A, Capella G, Del Giudice G, Palli D, Boeing H, Weikert C, Bueno-de-Mesquita HB, Carneiro F, Pala V, Vineis P, Tumino R, Panico S, Berglund G, Manjer J, Stenling R, Hallmans G, Martínez C, Dorronsoro M, Barricarte A, Navarro C, Quirós JR, Allen N, Key TJ, Bingham S, Linseisen J, Kaaks R, Overvad K, Tjønneland A, Büchner FL, Peeters PH, Numans ME, Clavel-Chapelon F, Boutron-Ruault MC, Trichopoulou A, Lund E, Slimani N, Ferrari P, Riboli E, González CA (2007) The association of gastric cancer risk with plasma folate, cobalamin, and methylenetetrahydrofolate reductase polymorphisms in the European Prospective Investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 16(11):2416–2424

    Article  PubMed  CAS  Google Scholar 

  • Weisberg I, Tran P, Christensen B, Sibani S, Rozen R (1998) A second genetic polymorphism in methylentetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 64(3):169–172

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hematology Department, Catholic University, L.go A. Gemelli 8, 00168, Rome, Italy

    Mariangela Palladino, Patrizia Chiusolo, Giovanni Reddiconto, Sara Marietti, Daniela De Ritis, Giuseppe Leone & Simona Sica

Authors
  1. Mariangela Palladino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrizia Chiusolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giovanni Reddiconto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sara Marietti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniela De Ritis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giuseppe Leone
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Simona Sica
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mariangela Palladino.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Palladino, M., Chiusolo, P., Reddiconto, G. et al. MTHFR Polymorphisms Involved in Vitamin B12 Deficiency Associated with Atrophic Gastritis. Biochem Genet 47, 645–650 (2009). https://doi.org/10.1007/s10528-009-9256-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-009-9256-0

Keywords

Search

Navigation