No evidence for AT2R gene derangement in human urinary tract anomalies
No evidence for AT2R gene derangement in human urinary tract anomalies
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DOI：
10.1046/j.1523-1755.2001.0590041244.x
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发表时间：
2001-04-01
影响因子：
19.6
通讯作者：
Mayumi, M
中科院分区：
文献类型：
--
作者：
Hiraoka, M;Taniguchi, T;Mayumi, M
背景资料。最近发现，位于X染色体上的血管紧张素2型受体(AT2R)基因突变的小鼠，特别是雄性小鼠，通常有一系列先天性肾脏和尿路异常(CAKUT)，包括肾脏发育不良，高加索男性输尿管肾盂连接部狭窄(UPJ)和多囊发育不良肾脏患者经常在AT2R基因内含子1发生A-G转换。我们先前发现肾发育不全在日本男孩中明显占优势。我们调查了每种CAKUT发生频率的性别比。比较了对照组和66例CAKUT日本男孩的A-G转换频率。肾发育不良16例，UPJ 17例，膀胱输尿管20例，其他异常13例。我们还调查了肾发育不良患者中是否存在A T2R基因突变。与AT2R基因突变的小鼠相比，人类患者的男女比例差异很大：肾发育不全16例，UPJ 2.1例，膀胱输尿管0.8例，其他1.2例。对照人群和CAKUT患者的A-G转换频率无差异[分别为30%(31/102)和35%(23/66)]。一项测序研究显示，在9名患有肾功能减退的男孩中没有突变。这些发现表明，AT2R基因在人类肾发育不良和其他CAKUT的发生中可能不起主要作用，至少在日本人中是这样。
Background. It has been recently found that mice, especially males, with a disrupted angiotensin type 2 receptor (AT2R) gene, which is located on the X-chromosome, often have a range of congenital anomalies of the kidney and urinary tract (CAKUT), including renal hypoplasia, and that Caucasian male patients with ureteropelvic junction stenosis (UPJ) and multicystic dysplastic kidneys frequently have A-G transition in intron 1 of the AT2R gene. We have previously found that renal hypoplasia is remarkably predominant in Japanese boys.Methods. We investigated sex ratios for the frequency of each CAKUT. The frequency of the A-G transition between the controls and 66 Japanese boys with CAKUT were compared. There was renal hypoplasia in 16, UPJ in 17, vesicoureteral in 20, and other anomalies in 13. We also investigated whether any mutations in A T2R genes were detectable in patients with renal hypoplasia.Results. In contrast to mice with a disruption of the AT2R gene, the male-to-female ratios in human patients proved to be considerably variable: 16 for renal hypoplasia, 2.1 for UPJ, 0.8 for vesicoureteral, and 1.2 for others. The frequency of the A-G transition was not different between the control population and the patients with CAKUT [31 of 102 (30%) vs. 23 of 66 (35%), respectively]. A sequencing study disclosed no mutations in nine boys with renal hypoplasia.Conclusions. These findings indicate that the AT2R gene may not play a major role in the development of renal hypoplasia and other CAKUT in humans, at least in the Japanese population.