title: Association of polymorphisms in DNMT1, DNMT3A, DNMT3B, MTHFR and MTRR genes with global DNA methylation levels and prognosis of autoimmune thyroid disease.
abstract: To clarify the association between factors regulating DNA methylation and the prognosis of autoimmune thyroid diseases (AITDs), we genotyped single nucleotide polymorphisms in genes encoding DNA methyltransferase 1 (DNMT1), DNMT3A, DNMT3B, methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), which are enzymes essential for DNA methylation. Subjects for this study included 125 patients with Hashimoto's disease (HD), including 48 patients with severe HD and 49 patients with mild HD; 176 patients with Graves' disease (GD), including 79 patients with intractable GD and 47 patients with GD in remission; and 83 healthy volunteers (control subjects). The DNMT1+32204GG genotype was more frequent in patients with intractable GD than in patients with GD in remission. Genomic DNA showed significantly lower levels of global methylation in individuals with the DNMT1+32204GG genotype than in those with the AA genotype. The MTRR+66AA genotype was observed to be more frequent in patients with severe HD than in those with mild HD. The DNMT1+14395A/G, DNMT3B-579G/T, MTHFR+677C/T and +1298A/C polymorphisms were not correlated with the development or prognosis of AITD. Our study indicates that the DNMT1+32204GG genotype correlates with DNA hypomethylation and with the intractability of GD, and that the MTRR+66AA genotype may correlate with the severity of HD.
authors.affiliation: Department of Biomedical Informatics, Division of Health Sciences Department of Laboratory Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Arakawa
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: N
authors.initials: N
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Sarumaru
authors.forename: Y
authors.initials: Y
authors.lastname: Hidaka
authors.forename: Y
authors.initials: Y
authors.lastname: Iwatani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005838:Genotype; D006111:Graves Disease / Q000201:enzymology / Q000235:genetics; D050031:Hashimoto Disease / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013967:Thyroiditis, Autoimmune / Q000201:enzymology / Q000235:genetics*; D055815:Young Adult; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C111241:methionine synthase reductase; C573423:MTHFR protein, human; C000619380:DNMT1 protein, human