Kelly H, Molony C M, Darlow J M, Pirker M E, Yoneda A, Green A J, Puri P, Barton D E
The National Centre for Medical Genetics, University College Dublin Department of Medical Genetics, Our Lady's Children's Hospital Crumlin, Dublin 12, Ireland.
J Med Genet. 2007 Nov;44(11):710-7. doi: 10.1136/jmg.2007.051086. Epub 2007 Jul 27.
Vesicoureteric reflux (VUR) is the retrograde flow of urine from the bladder into the ureters. It is the most common urological anomaly in children, and a major cause of end-stage renal failure and hypertension in both children and adults. VUR is seen in approximately 1-2% of Caucasian newborns and is frequently familial.
In order to search for genetic loci involved in VUR, we performed a genome-wide linkage scan using 4710 single-nucleotide polymorphisms (SNPs) in 609 individuals from 129 Irish families with >1 affected member.
Nonparametric linkage (NPL) analysis of the dataset yielded moderately suggestive linkage at chromosome 2q37 (NPL(max) = 2.67, p<0.001). Analysis of a subset without any additional features, such as duplex kidneys, yielded a maximum NPL score of 4.1 (p = 0.001), reaching levels of genome-wide statistical significance. Suggestive linkage was also seen at 10q26 and 6q27, and there were several smaller peaks.
Our results confirm the previous conclusion that VUR is genetically heterogeneous, and support the identification of several disease-associated regions indicated by smaller studies, as well as indicating new regions of interest for investigation.
膀胱输尿管反流（VUR）是指尿液从膀胱逆行流入输尿管。它是儿童中最常见的泌尿系统异常，也是儿童和成人终末期肾衰竭和高血压的主要原因。在大约1% - 2%的白种人新生儿中可见VUR，且常常具有家族性。
为了寻找与VUR相关的基因位点，我们对来自129个爱尔兰家庭、有超过1名患病成员的609名个体，使用4710个单核苷酸多态性（SNP）进行了全基因组连锁扫描。
对该数据集进行非参数连锁（NPL）分析，在2q37染色体上产生了中度提示性连锁（NPL（最大值） = 2.67，p < 0.001）。对一个没有任何其他特征（如重复肾）的子集进行分析，得到的最大NPL得分为4.1（p = 0.001），达到全基因组统计学显著水平。在10q26和6q27也观察到提示性连锁，并且有几个较小的峰值。
我们的结果证实了先前的结论，即VUR具有遗传异质性，并支持了一些较小规模研究所指出的几个疾病相关区域的鉴定，同时也指出了新的感兴趣的研究区域。
