Phenotypic heterogeneity and associations of two aldose reductase gene polymorphisms with nephropathy and retinopathy in type 2 diabetes

Phenotypic heterogeneity and associations of two aldose reductase gene polymorphisms with nephropathy and retinopathy in type 2 diabetes
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DOI:
10.2337/diacare.26.8.2410
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发表时间:
2003-08-01
期刊:
影响因子:
16.2
通讯作者:
Chan, JCN
Chan, JCN
中科院分区:
医学1区
文献类型:
--
作者:
Wang, Y;Ng, MCY;Chan, JCN

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目的-我们调查了糖尿病微血管并发症的表型特征及其与醛糖还原酶基因(ALR 2)5'区(CA)(n)微卫星和C/T多态性的相关性,研究设计和方法-在738名中国2型糖尿病患者的连续队列中,392名患者无糖尿病并发症,或无并发症,159例糖尿病肾病,66例糖尿病视网膜病变,121例糖尿病肾病和视网膜病变。肾病定义为两次尿白蛋白排泄率(AER)大于或等于20 μ g/min,白蛋白/肌酐比值大于或等于3.5 mg/mmol。视网膜病变的定义是存在视网膜病变、渗出物、激光标记和纤维增生或有玻璃体切除术史。结果:在整个队列中,糖尿病视网膜病变患者(n = 187)血压升高,BMI降低,而糖尿病肾病患者(n = 280)血压、腰臀比和血脂水平均高于无相应并发症的患者。糖尿病视网膜病变患者中(CA)(n)多态性的z+6携带者比无糖尿病视网膜病变患者(n = 551)更少(4.3% vs. 9.3%,P = 0.04)。CT/TT携带者的AER高于CC携带者(30.2 X/除以7.2 vs. 21.9 X/除以6.9 μ g/min,P = 0.03)。在排除无并发症的患者后,进行了进一步的亚组分析。
OBJECTIVE - We investigated the phenotypic features of diabetic microvascular complications and their association with a (CA)(n) microsatellite and a C/T polymorphism at the 5' region of the aldose reductase gene (ALR2) in a consecutive cohort of 738 Chinese type 2 diabetic patients.RESEARCH DESIGN AND METHODS - Of the entire patient cohort, 392 were free of diabetes complications, or uncomplicated, 159 had diabetic nephropathy, 66 had diabetic retinopathy, and 121 had both diabetic nephropathy and retinopathy. Nephropathy was defined as urinary albumin excretion rate (AER) greater than or equal to20 mug/min and albumin-to-creatinine ratio greater than or equal to3.5 mg/mmol in two urine collections. Retinopathy was defined by the presence of hemorrhages, exudates, laser marks, and fibrous proliferation or by a history of vitrectomy. (CA)(n) and C/T polymorphisms were examined by PCR followed by capillary electrophoresis and digestion with BfaI, respectively.RESULTS - in the whole cohort, patients with diabetic retinopathy (n = 187) had higher blood pressure and lower BMI, while those with diabetic nephropathy (n = 280) had higher blood pressure, waist-to-hip ratio, and lipid profile than those without the respective complications. The z+6 carriers of the (CA)(n) polymorphism were less common in patients with diabetic retinopathy than those without diabetic retinopathy (n = 551) (4.3 vs. 9.3%, P = 0.04). The CT/TT carriers had a higher AER than the CC carriers (30.2 X/divided by 7.2 vs. 21.9 X/divided by, 6.9 mug/min, P = 0.03). Further subgroup analysis was performed after excluding uncomplicated patients with