@article{3056636,
    title = "MTHFR gene variants and non-MALT lymphoma development in primary Sjogren's syndrome",
    author = "Fragkioudaki, S. and Nezos, A. and Souliotis, V.L. and Chatziandreou, I. and Saetta, A.A. and Drakoulis, N. and Tzioufas, A.G. and Voulgarelis, M. and Sfikakis, P.P. and Koutsilieris, M. and Crow, M.K. and Moutsopoulos, H.M. and Mavragani, C.P.",
    journal = "Scientific Reports",
    year = "2017",
    volume = "7",
    number = "1",
    publisher = "Nature Publishing Group",
    issn = "2045-2322",
    doi = "10.1038/s41598-017-07347-w",
    keywords = "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",
    abstract = "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)."
}