MTHFR gene variants and non-MALT lymphoma development in primary 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 ass...

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Autores principales: Sofia Fragkioudaki, Adrianos Nezos, Vassilis L. Souliotis, Ilenia Chatziandreou, Angelica A. Saetta, Nikolaos Drakoulis, Athanasios G. Tzioufas, Michael Voulgarelis, Petros P. Sfikakis, Michael Koutsilieris, Mary K. Crow, Haralampos M. Moutsopoulos, Clio P. Mavragani
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/3da35a06e8ad43e58ea639c207651de5
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spelling oai:doaj.org-article:3da35a06e8ad43e58ea639c207651de52021-12-02T12:30:35ZMTHFR gene variants and non-MALT lymphoma development in primary Sjogren’s syndrome10.1038/s41598-017-07347-w2045-2322https://doaj.org/article/3da35a06e8ad43e58ea639c207651de52017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07347-whttps://doaj.org/toc/2045-2322Abstract 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.Sofia FragkioudakiAdrianos NezosVassilis L. SouliotisIlenia ChatziandreouAngelica A. SaettaNikolaos DrakoulisAthanasios G. TzioufasMichael VoulgarelisPetros P. SfikakisMichael KoutsilierisMary K. CrowHaralampos M. MoutsopoulosClio P. MavraganiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sofia Fragkioudaki
Adrianos Nezos
Vassilis L. Souliotis
Ilenia Chatziandreou
Angelica A. Saetta
Nikolaos Drakoulis
Athanasios G. Tzioufas
Michael Voulgarelis
Petros P. Sfikakis
Michael Koutsilieris
Mary K. Crow
Haralampos M. Moutsopoulos
Clio P. Mavragani
MTHFR gene variants and non-MALT lymphoma development in primary Sjogren’s syndrome
description 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.
format article
author Sofia Fragkioudaki
Adrianos Nezos
Vassilis L. Souliotis
Ilenia Chatziandreou
Angelica A. Saetta
Nikolaos Drakoulis
Athanasios G. Tzioufas
Michael Voulgarelis
Petros P. Sfikakis
Michael Koutsilieris
Mary K. Crow
Haralampos M. Moutsopoulos
Clio P. Mavragani
author_facet Sofia Fragkioudaki
Adrianos Nezos
Vassilis L. Souliotis
Ilenia Chatziandreou
Angelica A. Saetta
Nikolaos Drakoulis
Athanasios G. Tzioufas
Michael Voulgarelis
Petros P. Sfikakis
Michael Koutsilieris
Mary K. Crow
Haralampos M. Moutsopoulos
Clio P. Mavragani
author_sort Sofia Fragkioudaki
title MTHFR gene variants and non-MALT lymphoma development in primary Sjogren’s syndrome
title_short MTHFR gene variants and non-MALT lymphoma development in primary Sjogren’s syndrome
title_full MTHFR gene variants and non-MALT lymphoma development in primary Sjogren’s syndrome
title_fullStr MTHFR gene variants and non-MALT lymphoma development in primary Sjogren’s syndrome
title_full_unstemmed MTHFR gene variants and non-MALT lymphoma development in primary Sjogren’s syndrome
title_sort mthfr gene variants and non-malt lymphoma development in primary sjogren’s syndrome
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/3da35a06e8ad43e58ea639c207651de5
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