Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes

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Santos-Bezerra, Daniele Pereira ^[1] ; Admoni, Sharon Nina ^{[1, 2]} ; Mori, Rosana Cristina ^[3] ; Pelaes, Tatiana Souza ^[1] ; Perez, Ricardo Vesoni ^[1] ; Machado, Cleide Guimaraes ^[4] ; Monteiro, Maria Beatriz ^[1] ; Parisi, Maria Candida ^[5] ; Pavin, Elizabeth Joao ^[5] ; Queiroz, Marcia Silva ^[2] ; Passarelli, Marisa ^[1] ; Machado, Ubiratan Fabres ^[3] ; Correa-Giannella, Maria Lucia ^{[6, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Clin Hosp, Lab Carbohydrates & Radioimuneassays LIM 18, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Clin Hosp, Div Endocrinol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Clin Hosp, Dept Physiol & Biophys, Inst Biomed Sci, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Med, Clin Hosp, Div Oftalmol, Sao Paulo - Brazil

^[5] State Univ Campinas UNICAMP, Dept Internal Med, Fac Med Sci, Campinas, SP - Brazil

^[6] Nove de Julho Univ UNINOVE, Dept Postgrad Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF DIABETES INVESTIGATION; v. 10, n. 4, p. 985-989, JUL 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 12/04831-1 - Novos moduladores do controle glicêmico e do desenvolvimento de complicações crônicas no Diabetes mellitus: perspectivas preventivas e terapêuticas
• Beneficiário: Ubiratan Fabres Machado
• Modalidade de apoio: Auxílio à Pesquisa - Temático