Laboratório de Carboidratos e Radioimunoensaio (LIM-18), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo. Av. Dr. Arnaldo, 455 - Sala: 3324, Sao Paulo, SP, 01246-903, Brazil.
Divisao de Oftalmologia, HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo. Av. Dr. Enéas de Carvalho Aguiar, 255 - sala: 6119, Sao Paulo, SP, 05403-900, Brazil.
Gene. 2019 Jun 30;703:120-124. doi: 10.1016/j.gene.2019.04.015. Epub 2019 Apr 5.
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.
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.
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.
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.
鉴于氧化应激参与糖尿病并发症的发病机制，我们评估了 1 型糖尿病（T1D）个体中，两种属于抗氧化谷胱甘肽（GSH）系统的基因调控区的功能性单核苷酸多态性（SNP）与糖尿病视网膜病变（DR）之间的关联：GCLC 中的 rs17883901 和 GPX4 中的 rs713041。
一项横断面病例对照研究纳入了 288 名个体（61%为女性，34[±11]岁，糖尿病病程 22[±9]年，均值[±标准差]），根据 DR 分期进行排序：无 DR（ADR）、非增殖性 DR（NPDR）和增殖性 DR（PDR）。采用实时 PCR 荧光标记探针进行 SNP 基因分型。采用调整混杂因素的逻辑回归模型进行分析。
在多分类回归模型（PDR 与 ADR）中，GCLC 中的 rs17883901 至少存在一个 T 等位基因是 PDR 的独立危险因素（OR 4.13，95%CI 1.38-13.66，p=0.014）。在女性 T1D 个体中，GPX4 中的 rs713041 至少存在一个 T 等位基因可降低 PDR 的发病风险（OR 0.30，95%CI 0.11-0.80，p=0.017）。
在研究的 T1D 个体人群中，功能性 SNPs rs17883901 和 rs713041 调节了 PDR 的发病风险，拓宽了候选基因的范围，为这种并发症的研究提供了更多可能。
