Genetic and epigenetic variants in the MTHFR gene are not associated with non-Hodgkin lymphoma

Autor: Larisa M. Haupt, Emily T. Camilleri, Rodney A. Lea, Lyn R. Griffiths, Heidi G. Sutherland, Gabrielle Bradshaw
Rok vydání: 2015
Předmět:
RFLP
restriction fragment length polymorphism
THF
tetrahydrofolate
HRM
high resolution melt
Biology
Article
FL
follicular lymphoma
PCR
polymerase chain reaction
677C > T polymorphism
immune system diseases
hemic and lymphatic diseases
Genotype
Genetics
medicine
Bp
base pairs
Epigenetics
Allele frequency
Genetics (clinical)
DNA
deoxyribose nucleic acid
Non-Hodgkin lymphoma
DNA methylation
EDTA
ethylenediaminetetra acetic acid
Methylation
CGIs
CpG Islands
SNP
single nucleotide polymorphism
medicine.disease
digestive system diseases
NHL
non-Hodgkin lymphoma
1298A > C polymorphism
Lymphoma
DLBCL
diffuse large b-cell lymphoma
OR
odds ratio
CpG site
CIMP
CpG island methylator phenotype
Methylenetetrahydrofolate reductase
MTHFR
Cancer research
biology.protein
WHO
World Health Organisation
MTHFR
methylenetetrahydrofolate reductase
SD
standard deviation
Zdroj: Meta Gene
ISSN: 2214-5400
DOI: 10.1016/j.mgene.2015.09.004
Popis: 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.
Highlights • The MTHFR gene codes for the MTHFR enzyme which plays a key role in folate and methionine metabolism • Polymorphisms affect its regulation and have been linked to lymphoma • No significant differences were observed between genotype or allele frequencies for two functional MTHFR polymorphisms • MTHFR promoter methylation is not an epigenetic biomarker for NHL diagnosis or prognosis in peripheral blood samples
Databáze: OpenAIRE
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