Association of polymorphisms in DNMT1, DNMT3A, DNMT3B, MTHFR and MTRR genes with global DNA methylation levels and prognosis of autoimmune thyroid disease

• Published in: Clinical and experimental immunology Vol. 170; no. 2; pp. 194 - 201
• Main Authors: Arakawa, Y., Watanabe, M., Inoue, N., Sarumaru, M., Hidaka, Y., Iwatani, Y.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2012; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Child; Deoxyribonucleic acid; Disease; DNA; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA Methylation; DNA Methyltransferase 3A; DNA Methyltransferase 3B; DNMT1; Endocrinopathies; Female; Ferredoxin-NADP Reductase - genetics; Fundamental and applied biological sciences. Psychology; Genes; Genotype; Graves Disease - enzymology; Graves Disease - genetics; Hashimoto Disease - enzymology; Hashimoto Disease - genetics; Humans; intractability; Male; Medical sciences; methylation; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Original; Polymorphism; Polymorphism, Single Nucleotide; Prognosis; severity; single nucleotide polymorphism; Thyroid. Thyroid axis (diseases); Thyroiditis, Autoimmune - enzymology; Thyroiditis, Autoimmune - genetics; Young Adult; Endocrinopathy; severity; Immunopathology; Methylenetetrahydrofolate reductase (NADPH); DNMT1; Prognosis; Genetic variability; intractability; Enzyme; Transferases; Thyroid diseases; Genotype; Autoimmune disease; Biochemistry; Association; [Methionine synthase]-cobalamin methyltransferase (cob(II)alamin reducing); Methyltransferases; Gene; DNA; Genetics; Oxidoreductases; Single nucleotide polymorphism; Methylation
• ISSN: 0009-9104; 1365-2249; 1365-2249
• DOI: 10.1111/j.1365-2249.2012.04646.x

Summary 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.