The thymidylate synthase enhancer region (TSER) polymorphism increases the risk of thymic lymphoid hyperplasia in patients with Myasthenia Gravis
| Autor: | Roberta Ricciardi, Melania Guida, Marco Lucchi, Alfredo Mussi, Angela Lopomo, Michelangelo Maestri, Franca Melfi, Fabio Coppedè, Lucia Migliore, Anna De Rosa |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Folate Receptors Nicotinic Nicotinic Thymidylate synthase 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase Lymphoid hyperplasia Genotype Receptors Promoter Regions Genetic biology General Medicine Single Nucleotide Hyperplasia Middle Aged Ferredoxin-NADP Reductase Enhancer Elements Genetic Myasthenia Gravis Polymorphisms Thymic hyperplasia Thymoma TYMS Adult Aged Female Genetic Predisposition to Disease Humans Methylenetetrahydrofolate Reductase (NADPH2) Thymidylate Synthase Thymus Hyperplasia Polymorphism Single Nucleotide Genetics medicine.symptom medicine.medical_specialty Enhancer Elements Promoter Regions 03 medical and health sciences Genetic Internal medicine medicine Polymorphism medicine.disease MTRR Myasthenia gravis 030104 developmental biology Endocrinology Methylenetetrahydrofolate reductase Cancer research biology.protein |
| Popis: | Background Myasthenia Gravis (MG) is caused, in approximately 80% of the patients, by autoantibodies against the nicotinic acetylcholine receptor (AChR). The disease is often associated with pathological changes of the thymus: thymic epithelial tumours are present in about 10–20% of the patients, while up to 80% of the patients with early disease onset have thymic hyperplasia. Folate metabolism is required for the production of DNA precursors and for proper DNA methylation reactions, and impaired folate metabolism has been often associated with cellular growth and cancer. Methods We investigated if major polymorphisms of folate-related genes, namely MTHFR c.677C > T, MTR c.2756A > G, MTRR c.66A > G and TYMS TSER (a 28-bp tandem repeat in the 5′ promoter enhancer region of TYMS) increase the risk of pathological changes of the thymus in AChR + MG patients. A total of 526 AChR + MG patients, including 132 patients with normal (involuted) thymus, 146 patients with thymic hyperplasia, and 248 patients with a thymoma were included in the study. Allele and genotype comparisons were performed among the three study groups, after correcting for multiple testing. Results The frequency of the TYMS TSER 3R allele was significantly higher in MG patients with thymic hyperplasia (P = 0.004), and the TYMS TSER 3R3R genotype was significantly associated with increased risk of thymic hyperplasia [OR 2.71 (95% CI: 1.34–5.47)]. Conclusions The 3R allele in the thymidylate synthase promoter enhancer region results in increased protein production, required for the synthesis of DNA precursors. The present study suggests that the TYMS TSER 3R allele increases the risk of thymic lymphoid hyperplasia in AChR + MG patients. |
| Databáze: | OpenAIRE |
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