To the best of our knowledge, this is the first report demonstrating that a functional polymorphism in the DNMT1 gene is related to methylation levels of DNA. In addition, The DNMT1+32204GG genotype was observed to be more frequent in patients with intractable GD than in those with GD in remission (Table 3). This indicates that

the +32204GG genotype, which is related to a lower level of global DNA methylation, is associated with the intractability of GD. In addition, we have reported previously that genetic programming GPCR & G Protein inhibitor for production of higher interleukin (IL)-1β and transforming growth factor (TGF)-β levels are associated with intractability of GD [26,27]. It is well known that demethylation of the CpG site in the promoter regions enhance gene expression [28,29]. Therefore, lowered global DNA click here methylation ability in individuals with the +32204GG genotype may decrease the methylation levels of IL1B and TGFB promoter regions and enhance the production of IL-1β and TGF-β. This may be a potential candidate mechanism to impede induction remission in GD patients with DNMT1+32204GG genotype. In addition, we clarified that the MTRR+66AA genotype was more frequent in

patients with severe HD than in those with mild HD. Previous reports showed that homocysteine levels were increased in plasma obtained from individuals with the MTRR+66AA genotype [21]. There are two possible mechanisms that may explain how the MTRR+66AA genotype is related to the severity of HD. One possibility is that increased homocysteine levels may cause an insufficient supply of methyl groups and result

in a decrease in global DNA methylation [24]. In this study, however, global methylation levels of DNA were not associated with the genotypes of the MTRR+66A/G polymorphism (Fig. 3). Another possibility is that an increase in homocysteine levels may increase caspase-3 activity and, thus, apoptosis in thyroid epithelial cells in HD patients with the MTRR+66AA genotype, as it has PJ34 HCl been reported that homocysteine induces caspase-3 activity and apoptosis in various cells [30–33]. Previous reports also suggest that caspase-3 is highly expressed in thyroid epithelial cells in HD patients [34]. In conclusion, the DNMT1+32204GG genotype is associated with hypomethylation of DNA and is related to the intractability of GD, while the MTRR+66A/G polymorphism is associated with the severity of HD. No potential conflicts of interest were disclosed. “
“Citation Li C, Qiao B, Zhan Y, Qi W, Chen Z-J. First evidence of genetic association between the MIF-173G/C single-nucleotide polymorphisms and polycystic ovary syndrome.