Department of Clinical Sciences-Diabetes and Endocrinology, Lund University Diabetes Centre, Clinical Research Centre, University Hospital Skane, UMAS, 20502 Malmo, Sweden.
Diabetologia. 2011 Sep;54(9):2295-302. doi: 10.1007/s00125-011-2178-5. Epub 2011 May 15.
AIMS/HYPOTHESIS: Several genome-wide linkage studies have shown an association between diabetic nephropathy and a locus on chromosome 18q harbouring two carnosinase genes, CNDP1 and CNDP2. Carnosinase degrades carnosine (β-alanyl-L-histidine), which has been ascribed a renal protective effect as a scavenger of reactive oxygen species. We investigated the putative associations of genetic variants in CNDP1 and CNDP2 with diabetic nephropathy (defined either as micro- or macroalbuminuria) and estimated GFR in type 2 diabetic patients from Sweden.
We genotyped nine single nucleotide polymorphisms (SNPs) and one trinucleotide repeat polymorphism (D18S880, five to seven leucine repeats) in CNDP1 and CNDP2 in a case-control set-up including 4,888 unrelated type 2 diabetic patients (with and without nephropathy) from Sweden (Scania Diabetes Registry).
Two SNPs, rs2346061 in CNDP1 and rs7577 in CNDP2, were associated with an increased risk of diabetic nephropathy (rs2346061 p = 5.07 × 10(-4); rs7577 p = 0.021). The latter was also associated with estimated GFR (β = -0.037, p = 0.014), particularly in women. A haplotype including these SNPs (C-C-G) was associated with a threefold increased risk of diabetic nephropathy (OR 2.98, 95% CI 2.43-3.67, p < 0.0001).
CONCLUSIONS/INTERPRETATION: These data suggest that common variants in CNDP1 and CNDP2 play a role in susceptibility to kidney disease in patients with type 2 diabetes.
目的/假设：几项全基因组连锁研究表明，糖尿病肾病与 18 号染色体上的一个基因座有关，该基因座包含两个肌肽酶基因，CNDP1 和 CNDP2。肌肽酶可降解肌肽（β-丙氨酰-L-组氨酸），它作为活性氧的清除剂具有肾脏保护作用。我们研究了 CNDP1 和 CNDP2 中的遗传变异与糖尿病肾病（定义为微量或大量白蛋白尿）的潜在关联，并估计了来自瑞典的 2 型糖尿病患者的估计肾小球滤过率（eGFR）。
我们在一个包括 4888 名来自瑞典（斯科讷糖尿病登记处）的无关 2 型糖尿病患者（有或无肾病）的病例对照研究中，对 CNDP1 和 CNDP2 中的 9 个单核苷酸多态性（SNP）和一个三核苷酸重复多态性（D18S880，5 到 7 个亮氨酸重复）进行了基因分型。
CNDP1 中的 rs2346061 和 CNDP2 中的 rs7577 两个 SNP 与糖尿病肾病的风险增加相关（rs2346061 p = 5.07×10(-4)；rs7577 p = 0.021）。后者还与估计的 eGFR 相关（β = -0.037，p = 0.014），特别是在女性中。包含这些 SNP 的单倍型（C-C-G）与糖尿病肾病的三倍风险相关（OR 2.98，95%CI 2.43-3.67，p < 0.0001）。
结论/解释：这些数据表明，CNDP1 和 CNDP2 中的常见变异在 2 型糖尿病患者的肾脏疾病易感性中起作用。
