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Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in females with Type 1 diabetes.

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 5 single nucleotide polymorphisms (SNPs) in the gene encoding DNA methytransferase 1 (DNMT1; rs8112895, rs7254567, rs11085721, rs17291414, and rs10854076) and their associations with diabetic kidney disease, retinopathy, distal polyneuropathy and autonomic cardiovascular neuropathy (CAN) in 359 long-term Type 1 diabetes individuals.

RESULTS: None of the studied SNPs 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 CAN in female individuals after adjustment for confounding variables (OR = 2.32; CI =1.26 - 4.33; P = 0.006).

CONCLUSIONS: The fact that heterozygous mutations in DNMT1 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 may predispose to more or less epigenetic changes in face of similar metabolic derangements triggered by hyperglycemia, constituting the "genetics of epigenetics" for microvascular diabetes complications. This article is protected by copyright. All rights reserved.

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