Whole-Genome Linkage and Association Scan in Primary, Nonsyndromic Vesicoureteric Reflux
Whole-Genome Linkage and Association Scan in Primary, Nonsyndromic Vesicoureteric Reflux
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DOI：
10.1681/asn.2009060624
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发表时间：
2010-01-01
影响因子：
13.6
通讯作者：
Goodship, Judith A.
中科院分区：
文献类型：
--
作者：
Cordell, Heather J.;Darlay, Rebecca;Goodship, Judith A.
原发性膀胱输尿管反流约占需要透析或移植的肾衰竭的10%，兄弟研究表明遗传因素很大。在这里，我们报告了原发性、非综合征性膀胱输尿管反流和反流肾病的全基因组连锁和关联扫描。我们使用连锁和基于家庭的关联方法分析了来自两个人群（英国和斯洛文尼亚）的320个白人家庭（661名患病个体，通常来自有两个患病兄弟姐妹的家庭）。我们发现了适度的关联证据，但与以前的研究没有明显的重叠。我们检测了6个候选基因（AGTR2、HNF1B、PAX2、RET、ROBO2和UPK3A）的相关性，但未检测到。基于家族的分析在英国家庭中检测到1个单核苷酸多态性（SNP），在斯洛文尼亚家庭中检测到3个SNP，在联合家庭中检测到3个SNP。病例对照分析检测到与另外三个snp相关。这项研究是迄今为止最大的反流遗传学研究，结果表明欧洲人群中可能不存在这种常见肾脏畸形的主要基因位点。
Primary vesicoureteric reflux accounts for approximately 10% of kidney failure requiring dialysis or transplantation, and sibling studies suggest a large genetic component. Here, we report a whole-genome linkage and association scan in primary, nonsyndromic vesicoureteric reflux and reflux nephropathy. We used linkage and family-based association approaches to analyze 320 white families (661 affected individuals, generally from families with two affected siblings) from two populations (United Kingdom and Slovenian). We found modest evidence of linkage but no clear overlap with previous studies. We tested for but did not detect association with six candidate genes (AGTR2, HNF1B, PAX2, RET, ROBO2, and UPK3A). Family-based analysis detected associations with one single-nucleotide polymorphism (SNP) in the UK families, with three SNPs in the Slovenian families, and with three SNPs in the combined families. A case-control analysis detected associations with three additional SNPs. The results of this study, which is the largest to date investigating the genetics of reflux, suggest that major loci may not exist for this common renal tract malformation within European populations.