International ISSN: 2471-0016 ICPJL

Clinical Pathology Journal
Editorial
Volume 1 Issue 3 - 2015
Future Perspectives in Genetics of Kidney Disease: Resistance Genes
Emile de Heer*
Department of Pathology, Leiden University Medical Center, The Netherlands
Received: October 27, 2015 | Published: October 30, 2015

*Corresponding author: Emile de Heer, Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands, Email:

Citation: Heer ED (2015) Future Perspectives in Genetics of Kidney Disease: Resistance Genes. Int Clin Pathol J 1(3): 00013. DOI: 10.15406/icpjl.2015.01.00013

Editorial

Patients with a systemic disorder such as primary hypertension, or diabetes can develop progressive kidney disease. The involvement of the kidney in these systemic disorders results in various forms of glomerulosclerosis and tubulo-interstitial fibrosis as common pathological features. This is accompanied by loss of renal function and increased cardiovascular mortality. However, the predisposition to develop kidney disease does not occur in all patients with a systemic disease. Epidemiological and genetic studies show that the predisposition to develop kidney disease in patients with a systemic disorder is genetically inherited. For most genetic studies whole genome association studies, gene expression profiles, and next generation sequencing have resulted in either identification of responsible genes, or mapping of the quantitative trait loci of candidate modifying genes. Since gene-association studies may contain false-positive reports, additional confirmation is usually required by a genetic meta-analysis to extract the correct genetic information [1-3]. Genetic association studies for susceptibility for focal segmental glomerulosclerosis [FSGS] show that this develops in 50% of patients with primary hypertension [4]. Meta-analysis of patients with diabetes show that at least 25 genes candidate genes are involved in the development of diabetic nephropathy that develops in 30-40% of these patients [3].

Animal studies in MWF rats with primary hypertension show that susceptibility to develop FSGS is determined by back ground genes from the rodent strain [5]. Consomic rat strains from susceptible strains with resistant strains show that primary hypertension resulting in FSGS are confined to QTLs on chromosome 6 and 8 from susceptible strains [6,7]. A recently reported novel explanation is the existence of genes that prevent development of progressive renal disease and protect the kidney for involvement in the systemic disease. Interesting information is provided by the ICGN mouse [8]. This tensin-2 deficient mouse strain develops progressive glomerulosclerosis and end stage renal disease. However when this genetic deficiency is transferred to mice from BL6, or 129 strains, the kidney disease does either not develops, or has a very mild course of disease [9]. By generating Consomic strains of chromosomes from resistant strains tot susceptible mice Sasaki and his colleagues show the existence of quantitative trait loci that confer resistance to renal disease [10]. If this finding applies to other systemic disorders like primary hypertension and diabetes, the therapeutic potential will be substantial. Identification of resistance-associated genes and their function will open possibilities to prevent or restore progressive kidney disease in large numbers of patients.

References

  1. Rahmattulla C, Mooyaart AL, van Hooven D, Schoones JW, Bruijn JA, et al. (2015) Genetic variants in ANCA-associated vasculitis: a meta-analysis. Ann Rheum Dis.
  2. Buurma AJ, Turner RJ, Driessen JH, Mooyaart AL, Schoones JW, et al. (2013) Genetic variants in pre-eclampsia: a meta-analysis. Hum Reprod Update 19(3): 289-303.
  3. Mooyaart AL, Valk EJ, van Es LA, Bruijn JA, De Heer E, et al. (2011) Genetic associations in diabetic nephropathy: a meta-analysis. Diabetologia 54(3): 544-553.
  4. Padmanabhan S, Caulfield M, Dominiczak AF (2015) Genetic and molecular aspects of hypertension. Circ Res 116: 937-959.
  5. Pravenec M, Kren V, Landa V, Mlejnek P, Musilova A, et al. (2014) Recent progress in the genetics of spontaneously hypertensive rats. Physiol Res 63(Suppl 1): 1-8.
  6. Schulz A, Kreutz R (2012) Mapping genetic determinants of kidney damage in rat models. Hypertens Res 35(7): 675-694.
  7. Van Es N, Schulz A, Ijpelaar D, van der Wal A, Kuhn K, et al. (2011) Elimination of severe albuminuria in aging hypertensive rats by exchange of 2 chromosomes in double-consomic rats. Hypertension 58(2): 219-224.
  8. Cho AR, Uchio YK, Torigai T, Miyamoto T, Miyoshi I, et al. (2006) Deficiency of the tensin2 gene in the ICGN mouse: an animal model for congenital nephrotic syndrome. Mamm Genome 17(5): 407-416.
  9. Nishino T, Sasaki N, Nagasaki K, Ichii O, Kon Y, et al. (2012) The 129 genetic background affects susceptibility to glomerulosclerosis in tensin2-deficient mice. Biomed Res 33(): 53-56.
  10. Sasaki H, Sasaki N, Nishino T, Nagasaki K, et al. (2014) Quantitative trait Loci for resistance to the congenital nephropathy in tensin 2-deficient mice. PLoS One 9(6): e99602.
© 2014-2016 MedCrave Group, All rights reserved. No part of this content may be reproduced or transmitted in any form or by any means as per the standard guidelines of fair use.
Creative Commons License Open Access by MedCrave Group is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work at http://medcraveonline.com
Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version | Opera |Privacy Policy