INSERM, Research Unit 695, Paris, France.
Mol Genet Metab. 2011 Dec;104(4):654-60. doi: 10.1016/j.ymgme.2011.08.033. Epub 2011 Sep 8.
Oxidative stress is involved in the pathophysiology of diabetic nephropathy. The superoxide dismutase (SOD) enzymes play a major role in detoxification of reactive oxygen species and have a protective effect against diabetic nephropathy. We investigated associations of allelic variations in SOD1 gene with nephropathy in patients with type 1 diabetes.
Seven SNPs in SOD1 region were analyzed in 1285 type 1 European Caucasian diabetic patients from the SURGENE prospective study (n=340; ten year follow-up), and the Genesis France-Belgium (n=501) and GENEDIAB (n=444) cross-sectional studies. Cox proportional hazards and logistic regression analyses were used to estimate hazard ratios or odds ratios for incidence and prevalence of diabetic nephropathy.
In the SURGENE study, the T-allele of rs1041740 was associated with the prevalence of incipient (OR 5.75, 95% CI 1.78-19.39, p=0.004) and established/advanced nephropathy at baseline (OR 8.95, 95% CI 1.51-58.42, p=0.02), and with the incidence of incipient nephropathy during follow-up (HR 1.46, 95% C.I. 1.13-1.90, p=0.004). The variant was also associated with decreased estimated glomerular filtration rate (eGFR) throughout the study. In cross-sectional study of Genesis/GENEDIAB cohorts, the G-allele of rs17880135 was associated with incipient (OR 7.53, 95% CI 2.30-25.45, p=0.001), established (OR 6.04, 95% CI 1.52-23.91, p=0.01) and advanced nephropathy (OR 10.03, 95% CI 2.95-35.44, p=0.0003).
SOD1 allelic variations were associated with the prevalence of diabetic nephropathy, with the incidence of microalbuminuria and with decreased eGFR in type 1 diabetic subjects. These results are consistent with an implication of oxidative stress in the pathophysiology of diabetic nephropathy and with the major role for antioxidant enzymes as a mechanism of renal protection.
氧化应激与糖尿病肾病的病理生理学有关。超氧化物歧化酶（SOD）在解毒活性氧方面发挥着重要作用，对糖尿病肾病具有保护作用。我们研究了 SOD1 基因的等位基因变异与 1 型糖尿病患者肾病的关系。
在 SURGENE 前瞻性研究（n=340；十年随访）中分析了 SOD1 区域的 7 个 SNP，以及 Genesis France-Belgium（n=501）和 GENEDIAB（n=444）的横断面研究。使用 Cox 比例风险和逻辑回归分析来估计糖尿病肾病发生率和患病率的风险比或优势比。
在 SURGENE 研究中，rs1041740 的 T 等位基因与初期（OR 5.75，95%CI 1.78-19.39，p=0.004）和基线时已建立/晚期肾病（OR 8.95，95%CI 1.51-58.42，p=0.02）以及随访期间初期肾病的发生率（HR 1.46，95%CI 1.13-1.90，p=0.004）相关。该变体还与整个研究过程中估算的肾小球滤过率（eGFR）降低有关。在 Genesis/GENEDIAB 队列的横断面研究中，rs17880135 的 G 等位基因与初期（OR 7.53，95%CI 2.30-25.45，p=0.001）、已建立（OR 6.04，95%CI 1.52-23.91，p=0.01）和晚期肾病（OR 10.03，95%CI 2.95-35.44，p=0.0003）相关。
SOD1 等位基因变异与 1 型糖尿病患者肾病的患病率、微量白蛋白尿的发生率以及 eGFR 的降低有关。这些结果与氧化应激在糖尿病肾病的病理生理学中的作用以及抗氧化酶作为肾脏保护机制的主要作用相一致。
