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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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-07347-w |
| _version_ | 1818429630733877248 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T15:20:35Z |
| format | Article |
| id | doaj.art-3da35a06e8ad43e58ea639c207651de5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T15:20:35Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3da35a06e8ad43e58ea639c207651de52022-12-21T22:56:10ZengNature PortfolioScientific Reports2045-23222017-08-01711810.1038/s41598-017-07347-wMTHFR gene variants and non-MALT lymphoma development in primary Sjogren’s syndromeSofia Fragkioudaki0Adrianos Nezos1Vassilis L. Souliotis2Ilenia Chatziandreou3Angelica A. Saetta4Nikolaos Drakoulis5Athanasios G. Tzioufas6Michael Voulgarelis7Petros P. Sfikakis8Michael Koutsilieris9Mary K. Crow10Haralampos M. Moutsopoulos11Clio P. Mavragani12Department of Physiology, School of Medicine, National and Kapodistrian University of AthensDepartment of Physiology, School of Medicine, National and Kapodistrian University of AthensInstitute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research FoundationDepartment of Pathology, School of Medicine, National and Kapodistrian University of AthensDepartment of Pathology, School of Medicine, National and Kapodistrian University of AthensResearch Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of AthensDepartment of Pathophysiology, School of Medicine, National and Kapodistrian University of AthensDepartment of Pathophysiology, School of Medicine, National and Kapodistrian University of AthensJoint Academic Rheumatology Program, National and Kapodistrian University of Athens, School of MedicineDepartment of Physiology, School of Medicine, National and Kapodistrian University of AthensMary Kirkland Center for Lupus Research, Hospital for Special Surgery, Weill Medical College of Cornell UniversityDepartment of Pathophysiology, School of Medicine, National and Kapodistrian University of AthensDepartment of Physiology, School of Medicine, National and Kapodistrian University of AthensAbstract 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.https://doi.org/10.1038/s41598-017-07347-w |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-07347-w |
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