The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease
The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease
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DOI：
10.1097/01.asn.0000013300.11876.37
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发表时间：
2002-05-01
影响因子：
13.6
通讯作者：
Harris, PC
中科院分区：
文献类型：
--
作者：
Rossetti, S;Burton, S;Harris, PC
主要形式常染色体显性多囊肾病 (PKD1) 中肾囊性疾病的严重程度差异很大。对 324 名具有突变特征的 PKD1 患者（80 个家庭）的临床数据进行了分析，以记录与肾脏结果相关的因素。终末期肾病 (ESRD) 的平均年龄为 54 岁。男性和女性之间无显着差异，且与血管紧张素转换酶多态性无关。观察到相当大的家庭内变异性，反映了遗传修饰因素和环境因素的影响。然而，家庭之间的结果也存在显着差异，罕见的异常晚发 PKD1 的例子。通过使用比例风险模型估计协变对 ESRD 时间的影响来评估可能的表型/基因型相关性。在总人群中，突变的位置（相对于中位位置；核苷酸 7812）而不是类型与 ESRD 发病年龄相关。 5' 区域突变的患者比 3' 区域突变的患者病情明显更严重：ESRD 的中位时间分别为 53 和 56 年（P = 0.025），60 岁时肾功能正常的机会不到一半（分别为 18.9% 和 39.7%）。这项研究表明 PKD1 突变的位置与早期 ESRD 显着相关，并质疑 PKD1 突变是否只是使该基因的所有产物失活。
The severity of renal cystic disease in the major form of autosomal dominant polycystic kidney disease (PKD1) is highly variable. Clinical data was analyzed from 324 mutation-characterized PKD1 patients (80 families) to document factors associated with the renal outcome. The mean age to end-stage renal disease (ESRD) was 54 yr. with no significant difference between men and women and no association with the angiotensin-converting enzyme polymorphism. Considerable intrafamilial variability was observed, reflecting the influences of genetic modifiers and environmental factors, However, significant differences in outcome were also found among families, with rare examples of unusually late-onset PKD1. Possible phenotype/genotype correlations were evaluated by estimating the effects of covariants on the time to ESRD using proportional hazards models. In the total population, the location of the mutation (in relation to the median position; nucleotide 7812), but not the type, was associated with the age at onset of ESRD. Patients with mutations in the 5' region had significantly more severe disease than the 3' group: median time to ESRD was 53 and 56 yr, respectively (P = 0.025), with less than half the chance of adequate renal function at 60 yr (18.9% and 39.7%, respectively). This study has shown that the position of the PKD1 mutation is significantly associated with earlier ESRD and questions whether PKD1 mutations simply inactivate all products of the gene.