Τίτλος:
MTHFR gene variants and non-MALT lymphoma development in primary Sjogren's syndrome
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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).
Συγγραφείς:
Fragkioudaki, S.
Nezos, A.
Souliotis, V.L.
Chatziandreou, I.
Saetta, A.A.
Drakoulis, N.
Tzioufas, A.G.
Voulgarelis, M.
Sfikakis, P.P.
Koutsilieris, M.
Crow, M.K.
Moutsopoulos, H.M.
Mavragani, C.P.
Περιοδικό:
Scientific Reports
Εκδότης:
Nature Publishing Group
Λέξεις-κλειδιά:
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
DOI:
10.1038/s41598-017-07347-w
