Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Diabetes. 2010 Jun;59(6):1555-9. doi: 10.2337/db09-1377. Epub 2010 Mar 23.
The 5-5 homozygous CNDP1 (carnosinase) genotype is associated with a reduced risk of diabetic nephropathy. We investigated whether this association is sex specific and independent of susceptibility for type 2 diabetes.
Three separate groups of 114, 90, and 66 patients with type 2 diabetes and diabetic nephropathy were included in this study and compared with 93 patients with type 2 diabetes for >15 years without diabetic nephropathy and 472 population control subjects. The diabetes control group was used to determine an association in the three patient groups separately, and the population control group was used to estimate the genotype risk [odds ratio (CI)] for the population in a pooled analysis. The population control subjects were also compared with 562 patients with type 2 diabetes without diabetic nephropathy to determine whether the association was independent of type 2 diabetes. The CNDP1 genotype was determined by fragment analysis after PCR amplification.
The frequency of the 5-5 homozygous genotype was 28, 36, and 41% in the three diabetic nephropathy patient groups and 43 and 42% in the diabetic and population control subjects, respectively. The 5-5 homozygous genotype occurred significantly less frequently in women in all three patient groups compared with diabetic control subjects. The genotype risk for the population was estimated to be 0.5 (0.30-0.68) in women and 1.2 (0.77-1.69) in men. The 562 patients with type 2 diabetes without diabetic nephropathy did not differ from the general population (P = 0.23).
This study suggests that the association between the CNDP1 gene and diabetic nephropathy is sex specific and independent of susceptibility for type 2 diabetes.
5-5 纯合子 CNDP1（肌肽酶）基因型与糖尿病肾病的风险降低相关。我们研究了这种相关性是否具有性别特异性且独立于 2 型糖尿病的易感性。
本研究纳入了三组分别患有 2 型糖尿病和糖尿病肾病的 114、90 和 66 例患者，并与 93 例患有 2 型糖尿病且病程>15 年但无糖尿病肾病的患者和 472 名对照人群进行比较。糖尿病对照组用于分别在三组患者中确定相关性，对照组用于在汇总分析中估计人群的基因型风险（比值比[CI]）。还将对照人群与 562 例患有 2 型糖尿病但无糖尿病肾病的患者进行比较，以确定该相关性是否独立于 2 型糖尿病。通过 PCR 扩增后的片段分析确定 CNDP1 基因型。
三组糖尿病肾病患者中 5-5 纯合子基因型的频率分别为 28%、36%和 41%，糖尿病和对照人群中分别为 43%和 42%。与糖尿病对照组相比，所有三组患者中的女性中 5-5 纯合子基因型的发生频率明显较低。该人群的基因型风险估计为女性 0.5（0.30-0.68），男性 1.2（0.77-1.69）。562 例患有 2 型糖尿病但无糖尿病肾病的患者与普通人群没有差异（P=0.23）。
本研究表明，CNDP1 基因与糖尿病肾病的相关性具有性别特异性且独立于 2 型糖尿病的易感性。
