Claudia Piona1, Silvia Costantini1, Chiara Zusi1, Tiziano Cozzini2, Emilio Pedrotti2, Marco Marigliano1, Elena Fornari1, Alice Maguolo1, Anita Morandi3, Claudio Maffeis1. 1. Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, Verona, P.le Stefani 1, 37126, Verona, Italy. 2. Department of Neuroscience, Biomedicine and Movement Sciences, Eye Clinic, University of Verona, P.le L. A. Scuro 10, 37134, Verona, Italy. 3. Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, Verona, P.le Stefani 1, 37126, Verona, Italy. anita.morandi@univr.it.
Abstract
BACKGROUND: Early ocular neurodegenerative signs of diabetic neuropathy (DN) can be found in children and adolescents with type 1 diabetes (T1D). No data are available on the potential role of polymorphisms in miRNAs genes in predisposing T1D subjects to these signs. AIMS: To determine whether MIR146A rs2910164 and MIR128A rs11888095 polymorphisms are associated with early retinal and corneal neurodegenerative changes in pediatric patients with T1D. METHODS: A total of 140 T1D children/adolescents underwent spectral domain-optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM) with measurement of retinal and corneal nerve fiber parameters. Risk factors for diabetes complications (diabetes duration, blood pressure, HbA1c) were recorded. Genotyping of rs2910164 and rs1188095 SNPs and genotype-phenotype association analysis were performed. RESULTS: The C allele of rs2910164 in MIR146A was associated with higher values of IVCM parameters and minimum rim width (MRW) of the peripapillary region of optic nerve head measured in the retina, whereas the T allele of rs1188095 in MIR128A was associated with a significant impairment of them. Multiple regression analysis showed that MIR146A and MIR128A polymorphisms were significantly associated with corneal nerve fiber length (beta = 0.225 and - 0.204, respectively) and other IVCM parameters, independently from age, diabetes duration, HbA1c and systolic blood pressure percentile. Similar results were found for MRW (beta = 0.213 and - 0.286, respectively). CONCLUSIONS: These results provide new insight into the genetic predisposition to DN showing that two polymorphisms in MIR146A and MIR128A genes could significantly contribute to the development of early ocular preclinical signs of DN.
BACKGROUND: Early ocular neurodegenerative signs of diabetic neuropathy (DN) can be found in children and adolescents with type 1 diabetes (T1D). No data are available on the potential role of polymorphisms in miRNAs genes in predisposing T1D subjects to these signs. AIMS: To determine whether MIR146A rs2910164 and MIR128A rs11888095 polymorphisms are associated with early retinal and corneal neurodegenerative changes in pediatric patients with T1D. METHODS: A total of 140 T1D children/adolescents underwent spectral domain-optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM) with measurement of retinal and corneal nerve fiber parameters. Risk factors for diabetes complications (diabetes duration, blood pressure, HbA1c) were recorded. Genotyping of rs2910164 and rs1188095 SNPs and genotype-phenotype association analysis were performed. RESULTS: The C allele of rs2910164 in MIR146A was associated with higher values of IVCM parameters and minimum rim width (MRW) of the peripapillary region of optic nerve head measured in the retina, whereas the T allele of rs1188095 in MIR128A was associated with a significant impairment of them. Multiple regression analysis showed that MIR146A and MIR128A polymorphisms were significantly associated with corneal nerve fiber length (beta = 0.225 and - 0.204, respectively) and other IVCM parameters, independently from age, diabetes duration, HbA1c and systolic blood pressure percentile. Similar results were found for MRW (beta = 0.213 and - 0.286, respectively). CONCLUSIONS: These results provide new insight into the genetic predisposition to DN showing that two polymorphisms in MIR146A and MIR128A genes could significantly contribute to the development of early ocular preclinical signs of DN.
Authors: Kim C Donaghue; M Loredana Marcovecchio; R P Wadwa; Emily Y Chew; Tien Y Wong; Luis Eduardo Calliari; Bedowra Zabeen; Mona A Salem; Maria E Craig Journal: Pediatr Diabetes Date: 2018-10 Impact factor: 4.866
Authors: Cristina Evangelisti; Maria Carolina Florian; Isabella Massimi; Carlo Dominici; Giuseppe Giannini; Silvia Galardi; Maria Cristina Buè; Simone Massalini; Heather P McDowell; Elio Messi; Alberto Gulino; Maria Giulia Farace; Silvia Anna Ciafrè Journal: FASEB J Date: 2009-08-27 Impact factor: 5.191