Allelic variations in genes belonging to glutathione system increase proliferative retinopathy risk in type 1 diabetes individuals

Autor(es)

Perez, Ricardo Vessoni ^[1] ; Machado, Cleide Guimaraes ^[2] ; Santos-Bezerra, Daniele Pereira ^[1] ; Admoni, Sharon Nina ^[1] ; Patente, Thiago Andrade ^[3] ; Monteiro, Maria Beatriz ^[1] ; Cavaleiro, Ana Mercedes ^[1] ; Queiroz, Marcia Silva ^[4] ; Nery, Marcia ^[4] ; Correa-Giannella, Maria Lucia ^{[1, 5]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Lab Carboidratos & Radioimunoensaio LIM 18, Ave Dr Arnaldo, 455 Sala 3324, BR-01246903 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Fac Med, Div Oftalmol, HCFMUSP, Ave Dr Eneas de Carvalho Aguiar, 255 Sala 6119, BR-05403900 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Dept Imunol, ICB, Lab Imunol Tumores, Ave Prof Lineu Prestes 730, BR-05508000 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Fac Med, Div Endocrinol, HCFMUSP, Ave Dr Eneas de Carvalho Aguiar, 255 Sala 7037, BR-05403900 Sao Paulo, SP - Brazil

^[5] Univ Nove Julho UNINOVE, Programa Posgrad Med, Rua Vergueiro 235, BR-01504001 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Gene; v. 703, p. 120-124, JUN 30 2019.
• Citações Web of Science: 0

Resumo

Aims: Given the participation of oxidative stress in the pathogenesis of diabetic complications, we evaluated, in type 1 diabetes (T1D) individuals, the association between diabetic retinopathy (DR) and functional single nucleotide polymorphisms (SNPs) in regulatory regions of two genes belonging to the antioxidant glutathione (GSH) system: rs17883901 in GCLC and rs713041 in GPX4. Methods: A cross-sectional case-control study included 288 individuals (61% women, 34{[}+/- 11] years old, diabetes duration of 22{[}+/- 9] years, mean {[}+/- SD]) sorted according to DR stages: absence of DR (ADR), non proliferative DR (NPDR) and proliferative DR (PDR). SNPs were genotyped by real-time PCR using fluorescent labelled probes. Logistic regression models with adjustment for confounding covariates were employed. Results: The presence of at least one T-allele of rs17883901 in GCLC was an independent risk factor for PDR (OR 4.13, 95% CI 1.38-13.66, p = 0.014) in a polytomous regression model (PDR versus ADR). The presence of at least one T-allele of rs713041 in GPX4 conferred protection against PDR (OR 0.30, 95% CI 0.11-0.80, p = 0.017) in female T1D individuals. Conclusion: The functional SNPs rs17883901 and rs713041 modulate the risk for PDR in the studied population of T1D individuals, widening the spectrum of candidate genes for this complication. (AU)

• Processo FAPESP: 09/09276-3 - Estudo de Polimorfismos em Genes que Codificam Enzimas Antioxidantes e Transportadores de Glicose e sua Associação com a Susceptibilidade a Complicações Crônicas em Pacientes Diabéticos Tipo 1
• Beneficiário: Maria Lucia Cardillo Corrêa Giannella
• Modalidade de apoio: Auxílio à Pesquisa - Regular