biostudies-literatureUnknown7(1)Fragkioudaki SPrimary 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. ?nalysis 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.Scientific reports7354https://www.ebi.ac.uk/biostudies/studies/S-EPMC5544668biostudies-literatureMTHFR gene variants and non-MALT lymphoma development in primary Sjogren's syndrome.PMC5544668Chatziandreou INezos AMavragani CPTzioufas AGMoutsopoulos HMVoulgarelis MSaetta AASfikakis PPKoutsilieris MFragkioudaki SDrakoulis NCrow MKSouliotis VLfalseMTHFR gene variants and non-MALT lymphoma development in primary Sjogren's syndrome.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. ?nalysis 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.2017-01-01T00:00:00Z2017 Aug2021-03-05T08:56:09Z2019-03-27T02:52:44ZS-EPMC55446682877918010.1038/s41598-017-07347-w