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Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in women 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. M...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626951/ https://www.ncbi.nlm.nih.gov/pubmed/30548403 http://dx.doi.org/10.1111/jdi.12988 |
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author | Santos‐Bezerra, 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 Correa‐Giannella, Maria Lucia |
author_facet | Santos‐Bezerra, 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 Correa‐Giannella, Maria Lucia |
author_sort | Santos‐Bezerra, Daniele Pereira |
collection | PubMed |
description | 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 (DNMT1; 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 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 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. |
format | Online Article Text |
id | pubmed-6626951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66269512019-07-17 Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes Santos‐Bezerra, 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 Correa‐Giannella, Maria Lucia J Diabetes Investig Articles 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 (DNMT1; 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 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 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. John Wiley and Sons Inc. 2019-02-01 2019-07 /pmc/articles/PMC6626951/ /pubmed/30548403 http://dx.doi.org/10.1111/jdi.12988 Text en © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Articles Santos‐Bezerra, 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 Correa‐Giannella, Maria Lucia Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes |
title | Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes |
title_full | Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes |
title_fullStr | Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes |
title_full_unstemmed | Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes |
title_short | Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes |
title_sort | genetic variants in dnmt1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626951/ https://www.ncbi.nlm.nih.gov/pubmed/30548403 http://dx.doi.org/10.1111/jdi.12988 |
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