Whole-genome linkage and association scan in primary, nonsyndromic vesicoureteric reflux.
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.
Cordell
Heather J
HJ
Institute of Human Genetics, Newcastle University, International Centre for Life, Newcastle upon Tyne, NE1 3BZ, UK.
Darlay
Rebecca
R
Charoen
Pimphen
P
Stewart
Aisling
A
Gullett
Ambrose M
AM
Lambert
Heather J
HJ
Malcolm
Sue
S
Feather
Sally A
SA
Goodship
Timothy H J
TH
Woolf
Adrian S
AS
Kenda
Rajko B
RB
Goodship
Judith A
JA
D016022:Case-Control Studies; D003627:Data Interpretation, Statistical; D008040:Genetic Linkage / Q000235:genetics*; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008562:Membrane Glycoproteins / Q000235:genetics; D051762:PAX2 Transcription Factor / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics; D035781:Siblings; D017524:Slovenia; D006113:United Kingdom; D060171:Uroplakin III; D014718:Vesico-Ureteral Reflux / Q000208:ethnology* / Q000235:genetics*; D000097905:Roundabout Proteins
D051539:Hepatocyte Nuclear Factor 1-beta; D008562:Membrane Glycoproteins; D051762:PAX2 Transcription Factor; D051096:Proto-Oncogene Proteins c-ret; D044139:Receptor, Angiotensin, Type 2; D011971:Receptors, Immunologic; D060171:Uroplakin III; C496495:HNF1B protein, human; C497318:PAX2 protein, human; C498890:ROBO2 protein, human; D000097905:Roundabout Proteins; C554660:UPK3A protein, human; C099282:RET protein, human