Haptoglobin genotype and renal function decline in type 1 diabetes.
Haptoglobin genotype and renal function decline in type 1 diabetes.
复制标题
DOI：
10.2337/db09-0874
复制
发表时间：
2009-12
期刊：
影响因子：
7.7
通讯作者：
Orchard TJ
中科院分区：
文献类型：
--
作者：
Costacou T;Ferrell RE;Ellis D;Orchard TJ
结合珠蛋白（Hp）结合游离Hb，抑制Hb诱导的氧化损伤。由于氧化应激与微血管并发症有关，我们评估了1型糖尿病中Hp基因型与微量白蛋白尿、大量白蛋白尿、终末期肾病（ESRD）和早期肾功能下降之间的关系。糖尿病并发症流行病学研究的参与者中有DNA可获得者被研究了微量白蛋白尿的发生率（白蛋白排泄率[AER] 20-200 μg/min），大量白蛋白尿（AER >200 μg/min），ESRD（肾透析或移植），肾功能下降（基线eGFR >60 ml/min的患者中，肾小球滤过率[eGFR]较基线下降≥30 ml/min/1.73 m2 [通过Cockcroft-Gault方程]估计）min/1.73 m2）。Hp 2/2、2/1和1/1基因型的比例分别为43.4%、44.4%和12.1%。在18年的随访中，eGFR下降、微量白蛋白尿、大量白蛋白尿和ESRD的发生率分别为42.0%、40.5%、16.7%和12.2%。Hp基因型之间无显著性单变量差异。然而，在多变量考克斯模型中，与Hp 1/1基因型相比，观察到Hp 2/2基因型eGFR下降（风险比1.79 [95% CI 1.06-3.00]）和ESRD（2.74 [1.17-6.45]）的风险增加了100倍;未观察到微量白蛋白尿或大量白蛋白尿的显著相关性。这些数据表明，虽然Hp基因型与蛋白尿本身无关，但它可能是早期肾功能下降和进展为ESRD的独立决定因素。了解这些明显矛盾的发现可能会提供进一步了解1型糖尿病肾病的发病机制。
Haptoglobin (Hp) binds free Hb, inhibiting Hb-induced oxidative damage. As oxidative stress has been associated with microvascular complications, we evaluated the relationship between Hp genotype and microalbuminuria, macroalbuminuria, end-stage renal disease (ESRD), and early renal function decline in type 1 diabetes. Participants from the Epidemiology of Diabetes Complications Study with DNA available were studied for the incidence of microalbuminuria (albumin excretion rate [AER] 20–200 μg/min), macroalbuminuria (AER >200 μg/min), ESRD (renal dialysis or transplantation), and renal function decline (a decline ≥30 ml/min per 1.73 m2 from baseline estimated [by the Cockcroft-Gault equation] glomerular filtration rate [eGFR] in those with baseline eGFR >60 ml/min per 1.73 m2). The proportions with the Hp 2/2, 2/1, and 1/1 genotype were 43.4, 44.4, and 12.1%, respectively. During 18 years of follow-up, the incidence of eGFR decline, microalbuminuria, macroalbuminuria, and ESRD was 42.0, 40.5, 16.7, and 12.2%, respectively. No significant univariate differences were observed by Hp genotype. However, in multivariable Cox models, an ∼twofold increased risk was observed for the Hp 2/2 compared with the Hp 1/1 genotype for eGFR decline (hazard ratio 1.79 [95% CI 1.06–3.00]) and ESRD (2.74 [1.17–6.45]); no significant associations were observed for microalbuminuria or macroalbuminuria. These data suggest that although Hp genotype is not associated with albuminuria per se, it may be an independent determinant of early renal function decline and progression to ESRD. Understanding these apparent contradictory findings may provide further insight into the pathogenesis of renal disease in type 1 diabetes.
登录
查看更多内容
影响因子：
13.2
作者：
Costacou, Tina;Ellis, Demetrius;Orchard, Trevor J.
通讯作者：
Orchard, Trevor J.
影响因子：
16.2
作者：
Lonn, E;Yusuf, S;Gerstein, HC
通讯作者：
Gerstein, HC
在体内和体外研究中，建立抗乳果蛋白是糖尿病血管疾病的主要易感基因。
影响因子：
2.9
作者：
Asleh, Rabea;Levy, Andrew P
通讯作者：
Levy, Andrew P
影响因子：
7.7
作者：
Baynes, JW;Thorpe, SR
通讯作者：
Thorpe, SR
影响因子：
120.7
作者：
Kramer, HJ;Nguyen, QD;Hsu, CY
通讯作者：
Hsu, CY