TY - JOUR
TI - MTHFR gene variants and non-MALT lymphoma development in primary Sjogren's syndrome
AU - Fragkioudaki, S.
AU - Nezos, A.
AU - Souliotis, V.L.
AU - Chatziandreou, I.
AU - Saetta, A.A.
AU - Drakoulis, N.
AU - Tzioufas, A.G.
AU - Voulgarelis, M.
AU - Sfikakis, P.P.
AU - Koutsilieris, M.
AU - Crow, M.K.
AU - Moutsopoulos, H.M.
AU - Mavragani, C.P.
JO - Scientific Reports
PY - 2017
VL - 7
TODO - 1
SP - null
PB - Nature Publishing Group
SN - 2045-2322
TODO - 10.1038/s41598-017-07347-w
TODO - methylenetetrahydrofolate reductase (NADPH2), allele;  complication;  disease predisposition;  DNA methylation;  female;  gene frequency;  genetic variation;  genetics;  genotype;  human;  male;  nonhodgkin lymphoma;  odds ratio;  prevalence;  single nucleotide polymorphism;  Sjoegren syndrome, Alleles;  Disease Susceptibility;  DNA Methylation;  Female;  Gene Frequency;  Genetic Variation;  Genotype;  Humans;  Lymphoma, Non-Hodgkin;  Male;  Methylenetetrahydrofolate Reductase (NADPH2);  Odds Ratio;  Polymorphism, Single Nucleotide;  Prevalence;  Sjogren's Syndrome
TODO - Primary Sjogren's syndrome (pSS) confers increased risk for non-Hodgkin lymphoma (NHL) development. Two common polymorphisms, the c. 677C > T and c. 1298A > C, of the methylene-tetrahydrofolate reductase (MTHFR) gene, an enzyme essential in DNA synthesis and methylation, have been associated with susceptibility to NHL. Herein, we tested the hypothesis that MTHFR variants contribute to pSS-related lymphomagenesis. 356 pSS patients, of whom 75 had MALT and 19 non-MALT NHL and 600 healthy controls were genotyped for the detection of MTHFR polymorphisms. DNA methylation levels were assessed by pyrosequencing of the LINE-1 retroelement promoter in DNA from 55 salivary gland tissues from pSS patients. DNA double-strand breaks were determined in peripheral blood mononuclear cells from 13 pSS patients, using comet assay. Αnalysis according to lymphoma subtype revealed increased frequency of c. 677C > T TT genotype and T allele, as well as reduced prevalence of the c. 1298A > C C allele in the pSS non-MALT group compared to controls and patients without NHL. MTHFR c. 677C > T TT genotype was associated with reduced DNA methylation levels, while MTHFR c. 1298A > C AC genotype with reduced DNA double-strand breaks levels. MTHFR variants may be involved in SS non-MALT NHL development, through contribution to defective DNA methylation and genomic instability. © 2017 The Author(s).
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