MTR 2756 A &gt; G polymorphism is associated with the risk of systemic lupus erythematosus in the Polish population

Burzynski, Michal; Duriagin, S.; Mostowska, M.; Wudarski, Mariusz; Chwalińska-Sadowska, H; Jagodzińśki, Paweł P.

doi:10.1177/0961203307077988

Cited by 25 publications

(18 citation statements)

References 36 publications

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“…Our results contrast with a smaller Italian study reporting that SLE patients had a higher prevalence of the MTHFR 677TT genotype 18 . A Polish study found that frequencies of MTHFR 677C>T were not different between SLE patients and controls, but the authors found that the MTR 2756G allele was overrepresented in SLE patients 32 , which contrasts with our finding of lack of an association.…”

Section: Discussioncontrasting

confidence: 99%

Functional Polymorphisms of Folate-Metabolizing Enzymes in Relation to Homocysteine Concentrations in Systemic Lupus Erythematosus

Summers¹,

Cucchiara²,

Nackos³

et al. 2008

J Rheumatol

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Objective To determine if functional polymorphisms of folate/homocysteine pathway enzymes are associated with homocysteine concentrations and/or coronary artery calcification (CAC) scores in patients with systemic lupus erythematosus (SLE) and controls. Methods We investigated 163 SLE patients and 160 controls. Functional polymorphisms in 6 genes in the folate/homocysteine pathway were genotyped: 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T, MTHFR 1298A>C, cystathionine ß-synthase (CBS) 844ins68, methionine synthase (MTR) 2756A>G, methionine synthase reductase (MTRR) 66A>G, thymidylate synthase (TYMS) 1494del6, and dihydrofolate reductase (DHFR) c.86+60_78. Results Homocysteine levels were higher in African American SLE patients than Caucasian patients and African American controls. Genotype distributions were significantly different in African American and Caucasian controls for 6 of the 7 polymorphisms. Genotype distributions for each polymorphism did not differ significantly between SLE patients and controls even after stratification by race. Glomerular filtration rate was strongly negatively correlated to homocysteine levels, and was therefore adjusted for as a covariate in the models of the effects of the polymorphisms on homocysteine levels. In SLE patients none of the 7 polymorphisms was associated with homocysteine concentrations. In Caucasian controls only MTHFR 677C>T and 1298A>C showed effects on homo-cysteine similar to what would be expected from the literature. There were no genotypic associations with median CAC scores in SLE patients or controls with and without stratification by race. Conclusion Polymorphisms in folate/homocysteine metabolizing enzymes do not predict higher homocysteine levels or CAC scores in patients with SLE.

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Section: Discussioncontrasting

confidence: 99%

Functional Polymorphisms of Folate-Metabolizing Enzymes in Relation to Homocysteine Concentrations in Systemic Lupus Erythematosus

Summers¹,

Cucchiara²,

Nackos³

et al. 2008

J Rheumatol

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“…RFX1, a transcription factor that affects DNA methylation and histone acetylation by recruiting the corepressors DNMT1 and histone deacetylase 1 to the promoters of methylation-sensitive genes, was reported to be decreased in SLE T cells (50). Gene polymorphisms of methionine synthase, which is located in chromosome 1q43, a region confirmed to confer risk for the development of SLE, have been linked to SLE (51). Binding of methyl binding domain proteins or methyl cytosine-binding proteins (MECPs) to demethylated promoter regions is known to represent an indirect gene-silencing mechanism by preventing the binding of transcription factors to the targeted gene promoter (52, 53).…”

Section: Discussionmentioning

confidence: 99%

Promoter Hypomethylation Results in Increased Expression of Protein Phosphatase 2A in T Cells from Patients with Systemic Lupus Erythematosus

Sunahori

Juang

Kyttaris

et al. 2011

The Journal of Immunology

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The catalytic subunit α isoform of protein phosphatase 2A (PP2Acα) activity, protein, and mRNA have been found increased in systemic lupus erythematosus (SLE) T cells and to contribute to decreased IL-2 production. The PP2Acα promoter activity is controlled epigenetically through the methylation of a CpG within a cAMP response element (CRE) motif defined by its promoter. We considered that hypomethylation may account for the increased expression of PP2Acα in patients with SLE. Using bisulfite sequencing, we found that SLE T cells displayed decreased DNA methylation in the promoter region compared with normal T cells. More importantly, we found that the CRE-defined CpG, which binds p-CREB, is significantly less methylated in SLE compared with normal T cells, and the levels of methylation correlated with decreased amounts of DNA methyltransferase 1 transcripts. Methylation intensity correlated inversely with levels of PP2Acα mRNA and SLE disease activity. Chromatin immunoprecipitation assays revealed more binding of p-CREB to the CRE site in SLE T cells, resulting in increased expression of PP2Acα. We propose that PP2Acα represents a new methylation-sensitive gene that, like the previously reported CD70 and CD11a, contributes to the pathogenesis of SLE.

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“…Many genes that encode proteins involved in the immune system have been designated as candidate susceptibility genes [17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

IL-18 105 A>C polymorphism contributes to renal manifestations in patients with SLE

et al. 2009

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SummarySystemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder characterized by various aberrations including increased production of IL-18.Since IL-18 105 A>C polymorphic variants have been linked to increased production of this cytokine, we investigated the prevalence of IL-18 105 A>C (rs549908) polymorphic variants in SLE patients (n=111) and controls (n=152).There were no significant differences in the distribution of IL-18 105 A>C polymorphic variants in SLE patients and controls. However, there was a significant association between the IL-18 105 AA genotype (recessive model) and renal manifestations OR=3.360 (1.523-7.415, P=0.0039) and the P value remained statistically significant after Bonferroni correction (P corr = 0.0351).Our findings indicate that the IL-18 105 AA genotype variant can contribute to renal manifestations in patients with SLE.

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MTR 2756 A > G polymorphism is associated with the risk of systemic lupus erythematosus in the Polish population

Cited by 25 publications

References 36 publications

Functional Polymorphisms of Folate-Metabolizing Enzymes in Relation to Homocysteine Concentrations in Systemic Lupus Erythematosus

Functional Polymorphisms of Folate-Metabolizing Enzymes in Relation to Homocysteine Concentrations in Systemic Lupus Erythematosus

Promoter Hypomethylation Results in Increased Expression of Protein Phosphatase 2A in T Cells from Patients with Systemic Lupus Erythematosus

IL-18 105 A>C polymorphism contributes to renal manifestations in patients with SLE

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