title: Association of the DNMT3B -579G>T polymorphism with risk of thymomas in patients with myasthenia gravis.
abstract: Increasing evidence suggests a contribution of epigenetic processes in promoting cancer and autoimmunity. Myasthenia gravis (MG) is an autoimmune disease mediated, in approximately 80% of the patients, by antibodies against the nicotinic acetylcholine receptor (AChR+). Moreover, epithelial tumours (thymomas) are present in about 10-20% of the patients, and there is indication that changes in DNA methylation might contribute to the risk and progression of thymomas. However, the role of epigenetics in MG is still not completely clarified. In the present study we investigated if a common polymorphism (-579G>T: rs1569686) in the promoter of the DNMT3B gene coding for the DNA methyltransferase 3B, an enzyme that mediates DNA methylation, increases the risk to develop MG or MG-associated thymomas. The study polymorphism was selected based on recent reports and a literature meta-analysis suggesting association with increased risk of various types of cancer. We screened 324 AChR+ MG patients (140 males and 184 females, mean age 56.0 ± 16.5 years) and 735 healthy matched controls (294 males and 441 females, mean age 57.3 ± 15.6 years). 94 of the total MG patients had a thymoma. While there was no association with the whole cohort of MG patients, we found a statistically significant association of the DNMT3B-579T allele (OR = 1.51; 95% CI=1.1-2.1, P = 0.01) and the TT homozygous genotype (OR = 2.59; 95% CI=1.4-4.9, P = 0.006) with the risk of thymoma. No association was observed in MG patients without thymoma, even after stratification into clinical subtypes. Present results suggest that the DNMT3B-579T allele might contribute to the risk of developing thymoma in MG patients, particularly in homozygous TT subjects.
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Coppedè
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricciardi
authors.forename: Maria
authors.initials: M
authors.lastname: Denaro
authors.forename: Anna
authors.initials: A
authors.lastname: De Rosa
authors.forename: Carlo
authors.initials: C
authors.lastname: Provenzano
authors.forename: Emanuela
authors.initials: E
authors.lastname: Bartoccioni
authors.forename: Angelo
authors.initials: A
authors.lastname: Baggiani
authors.forename: Marco
authors.initials: M
authors.lastname: Lucchi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mussi
authors.forename: Lucia
authors.initials: L
authors.lastname: Migliore
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D013945:Thymoma / Q000209:etiology*; D013953:Thymus Neoplasms / Q000209:etiology*; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D000097584:DNA Methyltransferase 3B