Persu Alexandre, El-Khattabi Ouarda, Messiaen Thierry, Pirson Yves, Chauveau Dominique, Devuyst Olivier
Division of Nephrology, Université Catholique de Louvain Medical School, 1200 Brussels, Belgium.
Nephrol Dial Transplant. 2003 Oct;18(10):2032-8. doi: 10.1093/ndt/gfg292.
The deleterious effect of the DD genotype of ACE in autosomal dominant polycystic kidney disease (ADPKD) remains controversial. Small sample size, population admixture and lack of consideration of parameters modulating the effects of ACE genotype, such as gender or alpha-adducin (ADD) genotype, might explain the discrepancy.
We investigated the effect of ACE (I/D) polymorphism on the age at end-stage renal disease (ESRD) in a homogeneous population of 191 ADPKD patients, according to gender and genotype for the G460W polymorphism of ADD. Cumulative renal survival was assessed in 276 patients from the same families.
Though no effect was detected in the whole population, analysis of the male subset (n = 97) showed that patients harbouring the DD genotype of ACE had a 5-year lower mean age at ESRD than DI + II patients [47.8 +/- 1.8 (n = 31) vs 52.8 +/- 1.1 (n = 66), respectively] (P = 0.02). Furthermore, cumulative renal survival was lower in the corresponding pedigrees [47 +/- 1 years, 95% confidence interval (CI) 45-49, vs 51 +/- 1 years, 95% CI 48-54]. The G460W polymorphism of ADD had no effect on the age at ESRD and cumulative renal survival, either alone or in combination with the ACE (I/D) polymorphism.
In this large series of ADPKD patients, we found no effect of the ACE (I/D) polymorphism on the age at ESRD, either alone or in combination with the G460W polymorphism of ADD. However, a deleterious effect of the DD genotype of ACE on renal disease progression was observed in ADPKD males.
血管紧张素转换酶（ACE）的DD基因型在常染色体显性遗传性多囊肾病（ADPKD）中的有害作用仍存在争议。样本量小、人群混合以及未考虑调节ACE基因型效应的参数（如性别或α-内收蛋白（ADD）基因型）可能解释了这种差异。
我们在191例ADPKD患者的同质人群中，根据性别和ADD的G460W多态性基因型，研究了ACE（I/D）多态性对终末期肾病（ESRD）年龄的影响。对来自同一家族的276例患者进行了累积肾脏生存率评估。
虽然在整个人群中未检测到影响，但对男性亚组（n = 97）的分析显示，携带ACE的DD基因型的患者ESRD的平均年龄比携带DI + II基因型的患者低5岁[分别为47.8 +/- 1.8岁（n = 31）和52.8 +/- 1.1岁（n = 66）]（P = 0.02）。此外，相应家系中的累积肾脏生存率较低[47 +/- 1岁，95%置信区间（CI）45 - 49，对比51 +/- 1岁，95%CI 48 - 54]。ADD的G460W多态性单独或与ACE（I/D）多态性联合对ESRD年龄和累积肾脏生存率均无影响。
在这一大系列ADPKD患者中，我们发现ACE（I/D）多态性单独或与ADD的G460W多态性联合对ESRD年龄均无影响。然而，在ADPKD男性中观察到ACE的DD基因型对肾脏疾病进展有有害作用。
