Genetic Variation in Antioxidant Response Modulates the Level of Oxidative Stress in Youth with Type 1 Diabetes and Poor Glycemic Control
Anita Morandi,
Massimiliano Corradi,
Chiara Zusi,
Claudia Piona,
Silvia Costantini,
Marco Marigliano,
Claudio Maffeis
Affiliations
Anita Morandi
Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, Piazzale Stefani, 37126 Verona, Italy
Massimiliano Corradi
Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, Piazzale Stefani, 37126 Verona, Italy
Chiara Zusi
Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, Piazzale Stefani, 37126 Verona, Italy
Claudia Piona
Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, Piazzale Stefani, 37126 Verona, Italy
Silvia Costantini
Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, Piazzale Stefani, 37126 Verona, Italy
Marco Marigliano
Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, Piazzale Stefani, 37126 Verona, Italy
Claudio Maffeis
Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, Piazzale Stefani, 37126 Verona, Italy
Background: The minor allele of the single nucleotide polymorphism (SNP) rs2364723 of NFE2L2, a gene encoding a master antioxidant transcription factor, has been associated with poor cardiovascular outcomes and with complications of type 2 diabetes. We assessed the association between rs2364723 of NFE2L2 and oxidative stress in children/adolescents with type 1 diabetes (T1D). Methods: In 384 children/adolescents with T1D (age 15.7 ± 3.2 years, 207 males), we assessed the oxidative stress by measuring the concentration of derivatives of reactive oxygen metabolites (d-ROMs) and we genotyped the rs2364723 SNP by real time polymerase chain reaction. Results: The concentration of d-ROMs was 372.8 ± 64.6 Carratelli units. The minor genotype (CC) of rs2364723 at NFE2L2 was associated with higher concentration of derivatives of d-ROMs in the subgroup with HbA1c ≥ 8% (B = 47.85, p for genotype ∗ HbA1c interaction = 0.019). Conclusions: The carriers of the minor genotype of rs2364723 may have increased oxidative stress compared to their counterparts with other genotypes, especially in case of poor glycemic control. This observation needs to be replicated and confirmed in larger independent cohorts of youth with T1D.
