Open AccessGenetic variants in DNMT 1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes
Author(s) -
SantosBezerra Daniele Pereira,
Admoni Sharon Nina,
Mori Rosana Cristina,
Pelaes Tatiana Souza,
Perez Ricardo Vesoni,
Machado Cleide Guimarães,
Monteiro Maria Beatriz,
Parisi Maria Candida,
Pavin Elizabeth Joao,
Queiroz Marcia Silva,
Passarelli Marisa,
Machado Ubiratan Fabres,
CorreaGiannella Maria Lucia
Publication year - 2019
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.12988
Subject(s) - medicine , epigenetics , single nucleotide polymorphism , diabetes mellitus , type 2 diabetes , population , bioinformatics , minor allele frequency , genetics , endocrinology , genotype , gene , biology , environmental health
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.