Rigoli Luciana, Chimenz Roberto, di Bella Chiara, Cavallaro Emanuela, Caruso Rosario, Briuglia Silvana, Fede Carmelo, Salpietro Carmelo Damiano
Department of Pediatrics, Genetics Unit, University School of Medicine, Messina, Italy.
Pediatr Res. 2004 Dec;56(6):988-93. doi: 10.1203/01.PDR.0000145252.89427.9E. Epub 2004 Oct 6.
Angiotensin I-converting enzyme (ACE) and angiotensin type 2 receptor (AT2R) gene polymorphisms have been associated with an increased incidence of congenital anomalies of the kidney and urinary tract (CAKUT). We investigated the genotype distribution of these polymorphisms in Italian children with CAKUT. We also evaluated the association between the ACE insertion/deletion and the AT2R gene polymorphisms with the progression of renal damage in subgroups of CAKUT patients. We recruited 102 Italian children with CAKUT; 27 with vesicoureteral reflux; 12 with hypoplastic kidneys; 20 with multicystic dysplastic kidneys; 13 with ureteropelvic junctions stenosis/atresia; 18 with nonobstructed, nonrefluxing primary megaureters; and 12 with posterior urethral valves and compared them with 92 healthy control subjects. ACE and AT2R gene polymorphisms were analyzed by PCR. The identification of AT2R gene polymorphisms in intron 1 and in exon 3 was revealed by enzymatic digestion. ACE genotype distribution in children with CAKUT was no different from that of the control subjects, but the subgroup of patients with radiographic renal parenchymal abnormalities showed an increased occurrence of the D/D genotype. The frequency of the G allele of AT2R gene in children with CAKUT was increased in respect to that of the control subjects. By contrast, no significant difference in the frequency of the C and A alleles of the AT2R gene was found. Our findings indicate that the ACE gene can be a risk factor in the progression of renal parenchymal damage in CAKUT patients. Moreover, a major role of the AT2R gene in the development of CAKUT has been found, at least in Italian children.
血管紧张素I转换酶（ACE）和血管紧张素2型受体（AT2R）基因多态性与先天性肾和尿路畸形（CAKUT）的发病率增加有关。我们调查了这些多态性在意大利CAKUT儿童中的基因型分布。我们还评估了ACE插入/缺失和AT2R基因多态性与CAKUT患者亚组中肾损伤进展之间的关联。我们招募了102名患有CAKUT的意大利儿童；27名患有膀胱输尿管反流；12名患有肾发育不全；20名患有多囊性发育不良肾；13名患有输尿管肾盂连接处狭窄/闭锁；18名患有无梗阻、无反流的原发性巨输尿管；以及12名患有后尿道瓣膜，并将他们与92名健康对照受试者进行比较。通过聚合酶链反应（PCR）分析ACE和AT2R基因多态性。通过酶切揭示了内含子1和外显子3中AT2R基因多态性的鉴定。CAKUT儿童的ACE基因型分布与对照受试者无差异，但有影像学肾实质异常的患者亚组中D/D基因型的发生率增加。与对照受试者相比，CAKUT儿童中AT2R基因G等位基因的频率增加。相比之下，未发现AT2R基因C和A等位基因频率有显著差异。我们的研究结果表明，ACE基因可能是CAKUT患者肾实质损伤进展的危险因素。此外，至少在意大利儿童中，已发现AT2R基因在CAKUT的发生中起主要作用。
