Inserm Research Unit 695, 16 rue Henri Huchard, 75018, Paris, France.
Diabetologia. 2013 Dec;56(12):2733-42. doi: 10.1007/s00125-013-3057-z. Epub 2013 Sep 21.
AIMS/HYPOTHESIS: Oxidative stress is involved in the pathogenesis of diabetic nephropathy. The antioxidant enzyme catalase plays a key role in redox regulation in the kidney. We investigated associations of catalase gene (CAT) polymorphisms and plasma catalase activity with diabetic nephropathy in type 1 diabetic patients.
We genotyped nine single nucleotide polymorphisms (SNPs) in the CAT region in participants from the Survival Genetic Nephropathy (SURGENE) (340 French participants, 10 year follow-up) and the Génétique de la Néphropathie Diabétique (GENEDIAB) (444 Belgian and French participants, 8 year follow-up) study cohorts. Replication was performed in a Brazilian cross-sectional cohort (n = 451). Baseline plasma catalase activity was measured in SURGENE (n = 120) and GENEDIAB (n = 391) participants.
The A allele of rs7947841 was associated with the prevalence of incipient (OR 2.79, 95% CI 1.21, 6.24, p = 0.01) and established or advanced nephropathy (OR 5.72, 95% CI 1.62, 22.03, p = 0.007), and with the incidence of renal events, which were defined as new cases of microalbuminuria or progression to a more severe stage of nephropathy during follow-up (HR 1.82, 95% CI 1.13, 2.81, p = 0.01) in SURGENE participants. The same risk allele was associated with incipient nephropathy (OR 3.13, 95% CI 1.42, 7.24, p = 0.004) and with the incidence of end-stage renal disease (ESRD) (HR 2.11, 95% CI 1.23, 3.60, p = 0.008) in GENEDIAB participants. In both cohorts, the risk allele was associated with lower catalase activity. Associations with incipient and established or advanced nephropathy were confirmed in the replication cohort.
CONCLUSIONS/INTERPRETATION: CAT variants were associated with the prevalence and incidence of diabetic nephropathy and ESRD in type 1 diabetic patients. Our results confirm the protective role of catalase against oxidative stress in the kidney.
目的/假设：氧化应激参与了糖尿病肾病的发病机制。抗氧化酶过氧化氢酶在肾脏的氧化还原调节中起着关键作用。我们研究了过氧化氢酶基因（CAT）多态性和血浆过氧化氢酶活性与 1 型糖尿病患者糖尿病肾病的关系。
我们在来自生存遗传肾病（SURGENE）（340 名法国参与者，10 年随访）和糖尿病肾病遗传学（GENEDIAB）（444 名比利时和法国参与者，8 年随访）研究队列的参与者的 CAT 区域中对 9 个单核苷酸多态性（SNP）进行了基因分型。在巴西的一个横断面队列（n=451）中进行了复制。在 SURGENE（n=120）和 GENEDIAB（n=391）参与者中测量了基线血浆过氧化氢酶活性。
rs7947841 的 A 等位基因与初发（OR 2.79，95%CI 1.21，6.24，p=0.01）和已确诊或晚期肾病（OR 5.72，95%CI 1.62，22.03，p=0.007）以及肾脏事件的发生率相关，肾脏事件定义为随访期间新出现微量白蛋白尿或肾病恶化更严重阶段的病例（HR 1.82，95%CI 1.13，2.81，p=0.01）在 SURGENE 参与者中。相同的风险等位基因与初发肾病（OR 3.13，95%CI 1.42，7.24，p=0.004）和终末期肾病（ESRD）（HR 2.11，95%CI 1.23，3.60，p=0.008）的发生率相关，在 GENEDIAB 参与者中。在两个队列中，风险等位基因均与过氧化氢酶活性降低相关。在复制队列中，与初发和已确诊或晚期肾病的关联得到了证实。
结论/解释：CAT 变体与 1 型糖尿病患者糖尿病肾病和 ESRD 的患病率和发生率相关。我们的结果证实了过氧化氢酶在肾脏对抗氧化应激的保护作用。
