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Aims/Introduction  Epigenetics participate in the pathogenesis of metabolic memory, a situation in which hyperglycemia exerts prolonged deleterious effects even after its normalization. We tested the hypothesis that genetic variants in an epigenetic gene could predispose to diabetes complications.    Material and Methods  We assessed the frequency of five single‐nucleotide polymorphisms in the gene encoding  deoxyribonucleic acid  methytransferase 1 (  DNMT 1;  rs8112895, rs7254567, rs11085721, rs17291414 and rs10854076), and their associations with diabetic kidney disease, retinopathy, distal polyneuropathy and autonomic cardiovascular neuropathy in 359 individuals with long‐term type 1 diabetes.    Results  None of the single‐nucleotide polymorphisms studied was significantly associated with the presence of chronic complications in the overall population. However, after sex stratification, the minor allele C of rs11085721 conferred risk for  cardiovascular neuropathy  in women after adjustment for confounding variables (odds ratio 2.32; 95% confidence interval 1.26–4.33;  P  =   0.006).    Conclusions  The fact that heterozygous mutations in   DNMT 1  are associated with hereditary sensory autonomic neuropathy provides plausibility to the present finding. If confirmed in independent samples, it suggests that genetic variants in epigenetic genes might predispose to more or fewer epigenetic changes in the face of similar metabolic derangements triggered by hyperglycemia, constituting the “genetics of epigenetics” for microvascular diabetes complications.

Genetic variants in DNMT 1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes