title: Genetic and epigenetic variants in the MTHFR gene are not associated with non-Hodgkin lymphoma.
abstract: The methylenetetrahydrofolate reductase (MTHFR) gene codes for the MTHFR enzyme which plays a key role in the pathway of folate and methionine metabolism. Polymorphisms of genes in this pathway affect its regulation and have been linked to lymphoma. In this study we examined whether we could detect an association between two common non-synonymous MTHFR polymorphisms, 677C > T (rs1801133) and 1298A > C (rs1801131), and susceptibility to non-Hodgkin lymphoma (NHL) in an Australian case-control cohort. We found no significant differences between genotype or allele frequencies for either polymorphisms between lymphoma cases and controls. We also explored whether epigenetic modification of MTHFR, specifically DNA methylation of a CpG island in the MTHFR promoter region, is associated with NHL using blood samples from patients. No difference in methylation levels was detected between the case and control samples suggesting that although hypermethylation of MTHFR has been reported in tumour tissues, particularly in the diffuse large B-cell lymphoma subtype of NHL, methylation of this MTHFR promoter CpG island is not a suitable epigenetic biomarker for NHL diagnosis or prognosis in peripheral blood samples. Further studies into epigenetic variants could focus on genes that are robustly associated with NHL susceptibility.
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane QLD, Australia.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Bradshaw
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane QLD, Australia.
authors.forename: Heidi G
authors.initials: HG
authors.lastname: Sutherland
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane QLD, Australia.
authors.forename: Emily T
authors.initials: ET
authors.lastname: Camilleri
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane QLD, Australia.
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Lea
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane QLD, Australia.
authors.forename: Larisa M
authors.initials: LM
authors.lastname: Haupt
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane QLD, Australia.
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
keywords: 1298A > C polymorphism; 677C > T polymorphism; Bp, base pairs; CGIs, CpG Islands; CIMP, CpG island methylator phenotype; DLBCL, diffuse large b-cell lymphoma; DNA methylation; DNA, deoxyribose nucleic acid; EDTA, ethylenediaminetetra acetic acid; FL, follicular lymphoma; HRM, high resolution melt; MTHFR; MTHFR, methylenetetrahydrofolate reductase; NHL, non-Hodgkin lymphoma; Non-Hodgkin lymphoma; OR, odds ratio; PCR, polymerase chain reaction; RFLP, restriction fragment length polymorphism; SD, standard deviation; SNP, single nucleotide polymorphism; THF, tetrahydrofolate; WHO, World Health Organisation