AIMS/HYPOTHESIS:Type 2 diabetes is a chronic metabolic disorder associated with devastating microvascular complications. Genome-wide association studies have identified more than 60 genetic variants associated with type 2 diabetes and/or glucose and insulin traits, but their role in the progression of diabetes is not established. The aim of this study was to explore whether these variants were also associated with the development of nephropathy in patients with type 2 diabetes.
METHODS:We studied 28 genetic variants in 2,229 patients with type 2 diabetes from the local Malmö Scania Diabetes Registry (SDR) published during 2007-2010. Diabetic nephropathy (DN) was defined as micro- or macroalbuminuria and/or end-stage renal disease. Estimated glomerular filtration rate (eGFR) was assessed using the MDRD-4 formula. Replication genotyping of rs1531343 was performed in diabetic (Steno type 2 diabetes [n = 345], Genetics of Diabetes Audit and Research in Tayside Scotland [Go-DARTS] [n = 784]) and non-diabetic (Malmö Preventive Project [n = 2,523], Botnia study [n = 2,247]) cohorts.
RESULTS:In the SDR, HMGA2 single-nucleotide polymorphism rs1531343 was associated with DN (OR 1.50, 95% CI 1.20, 1.87, p = 0.00035). In the combined analysis totalling 3,358 patients with type 2 diabetes (n = 1,233 cases, n = 2,125 controls), carriers of the C-allele had a 1.45-fold increased risk of developing nephropathy (95% CI 1.20, 1.75, p = 0.00010). Furthermore, the risk C-allele was associated with lower eGFR in patients with type 2 diabetes (n = 2,499, β ± SEM, -3.7 ± 1.2 ml/min, p = 0.002) and also in non-diabetic individuals (n = 17,602, β ± SEM, -0.008 ± 0.003 ml/min (log( e )), p = 0.006).
CONCLUSIONS/INTERPRETATION:These data demonstrate that the HMGA2 variant seems to be associated with increased risk of developing nephropathy in patients with type 2 diabetes and lower eGFR in both diabetic and non-diabetic individuals and could thus be a common denominator in the pathogenesis of type 2 diabetes and kidney complications.
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【Common variant in the HMGA2 gene increases susceptibility to nephropathy in patients with type 2 diabetes.].
【HMGA2基因的常见变异会增加2型糖尿病患者对肾病的易感性。】
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DOI：10.1007/s00125-012-2760-5文章类型：杂志文章
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目的/假设：2型糖尿病是与破坏性微血管并发症相关的慢性代谢性疾病。全基因组关联研究已鉴定出与2型糖尿病和/或葡萄糖和胰岛素性状相关的60多种遗传变异，但尚未确定它们在糖尿病进展中的作用。这项研究的目的是探讨这些变异是否也与2型糖尿病患者的肾病发展有关。
方法：我们研究了2007年至2010年间发表的2 229例2型糖尿病患者的28种遗传变异，这些变异来自当地的马尔默斯堪尼亚糖尿病登记处（SDR）。糖尿病性肾病（DN）被定义为微蛋白尿或巨蛋白尿和/或晚期肾病。使用MDRD-4公式评估估计的肾小球滤过率（eGFR）。 rs1531343的复制基因分型是在糖尿病（Steno 2型糖尿病[n = 345]，Tayside Scotland糖尿病的遗传学研究和研究[Go-DARTS] [n = 784]）和非糖尿病（Malmö预防项目[n == 2,523]，Botnia研究[n = 2,247]队列。
结果：在SDR中，HMGA2单核苷酸多态性rs1531343与DN相关（OR 1.50，95％CI 1.20，1.87，p = 0.00035）。在总共3358名2型糖尿病患者的综合分析中（n = 1,233例，n = 2,125对照），C-等位基因携带者患肾病的风险增加了1.45倍（95％CI 1.20，1.75，p = 0.00010 ）。此外，高风险C等位基因与2型糖尿病患者的eGFR较低有关（n = 2,499，β±SEM，-3.7±1.2 ml / min，p = 0.002），在非糖尿病患者中（n = 17,602） ，β±SEM，-0.008±0.003 ml / min（log（e）），p = 0.006）。
结论/解释：这些数据表明，HMGA2变异似乎与2型糖尿病患者发生肾病的风险增加以及糖尿病和非糖尿病患者的eGFR降低有关，因此可能是2型糖尿病发病机制的共同指标2糖尿病和肾脏并发症。
方法：我们研究了2007年至2010年间发表的2 229例2型糖尿病患者的28种遗传变异，这些变异来自当地的马尔默斯堪尼亚糖尿病登记处（SDR）。糖尿病性肾病（DN）被定义为微蛋白尿或巨蛋白尿和/或晚期肾病。使用MDRD-4公式评估估计的肾小球滤过率（eGFR）。 rs1531343的复制基因分型是在糖尿病（Steno 2型糖尿病[n = 345]，Tayside Scotland糖尿病的遗传学研究和研究[Go-DARTS] [n = 784]）和非糖尿病（Malmö预防项目[n == 2,523]，Botnia研究[n = 2,247]队列。
结果：在SDR中，HMGA2单核苷酸多态性rs1531343与DN相关（OR 1.50，95％CI 1.20，1.87，p = 0.00035）。在总共3358名2型糖尿病患者的综合分析中（n = 1,233例，n = 2,125对照），C-等位基因携带者患肾病的风险增加了1.45倍（95％CI 1.20，1.75，p = 0.00010 ）。此外，高风险C等位基因与2型糖尿病患者的eGFR较低有关（n = 2,499，β±SEM，-3.7±1.2 ml / min，p = 0.002），在非糖尿病患者中（n = 17,602） ，β±SEM，-0.008±0.003 ml / min（log（e）），p = 0.006）。
结论/解释：这些数据表明，HMGA2变异似乎与2型糖尿病患者发生肾病的风险增加以及糖尿病和非糖尿病患者的eGFR降低有关，因此可能是2型糖尿病发病机制的共同指标2糖尿病和肾脏并发症。
