A Promoter Polymorphism of the Alpha 8 Integrin Gene and the Progression of Autosomal-Dominant Polycystic Kidney Disease

Language
en
Document Type
Article
Issue Date
2013-03-14
Issue Year
2007
Authors
Zeltner, Raoul
Hilgers, Karl F.
Schmieder, Roland E.
Porst, Markus
Schulze, Bernd D.
Hartner, Andrea
Editor
Abstract

Background/Aims: Dysregulation of integrins is a feature of tissue remodeling in autosomal-dominant polycystic kidney disease (ADPKD). The alpha 8 beta 1 integrin ( _ 8 _ 1) affects kidney development and the susceptibility to renal injury in mice. We investigated whether the –414 T/C polymorphism in the promoter region of the alpha 8 integrin chain gene (ITGA8) is associated with the progression of renal disease in ADPKD. Methods: Genotyping for the –414 T/C polymorphism was performed by allelic separation using RT-PCR in 294 patients with ADPKD. Alpha 8 integrin expression was detected by RT-PCR and immunohistochemistry. Results: 41% of the study population reached end stage renal disease at a mean age of 51 8 12 years. The frequency of the –414 C allele was 0.194 in ADPKD. C allele carriers (CC and TC genotypes) were compared with patients homozygous for the T allele (TT genotype). Kaplan-Meier analysis revealed that end-stage renal failure occurred at a significantly younger age in TT homozygotes (median age, 47 years; 95% CI, 46–49 years) than in C allele carriers (median age, 51 years; 95% CI, 49–53 years; p = 0.046 by the log-rank test). When parameters of ADPKD patients were compared between genotype by analysis of variance, only age at onset of end-stage renal failure was significantly different (p = 0.026) whereas age at onset of hypertension, body surface area, 24-hour systolic and diastolic blood pressure did not differ. In kidneys of ADPKD, expression of alpha 8 integrin is increased and found de novo in cystic epithelia. Conclusion: A polymorphism of the ITGA8 promoter modifies the progression of renal failure in ADPKD.

Journal Title
Nephron Clinical Practice 2008; 108: c169-c175. <http://content.karger.com/ProdukteDB/produkte.asp?typ=pdf&doi=116887> © 2008 S. Karger AG, Basel
Citation

Nephron Clinical Practice 2008; 108: c169-c175. http://content.karger.com/ProdukteDB/produkte.asp?typ=pdf&doi=116887 © 2008 S. Karger AG, Basel

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