Genetic Predisposition Factors in Renal Disorders
Rad IA
*
Department of Medical Genetics, Motahari Teaching Hospital, Urmia University of Medical Sciences, Urmia, West Azerbaijan, Iran
*
Corresponding author: Isa Abdi Rad, MD PhD, Department of Medical Genetics, Motahari Teaching Hospital, Urmia University of Medical Sciences, Kashani Street,
Urmia, West Azerbaijan, Iran, Tel: +98-44-32240166/+914 440 5829; E-mail: isaabdirad@yahoo.com
Received date: July 11, 2017; Accepted date: July 12, 2017; Published date: July 14, 2017
Copyright: © 2017 Rad IA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original author and source are credited.
Citation: Rad IA (2017) Genetic Predisposition Factors in Renal Disorders. J Kidney 3: e109. doi:10.4172/2472-1220.1000e109
Editorial
Genetic susceptibility plays an important role in the development of
many renal disorders. Revealing the etiologic basis and predisposing
factors of renal disorders have impacts on the prevention of these
prevalent disorders which have a global health burden with a high
economic cost. Prevention of renal diseases also has impact on the
prevention of other disorders since renal diseases can cause other
health problems such as heart disease. Te fundamental basis of
prevention is determination of predisposing factors especially genetic
factors, because by recognition of genetic basis of the disease,
prevention can be applied in the prenatal period.
Some renal disorders are single gene disorders with obvious
Mendelian inheritance such as polycystic kidney diseases. Autosomal-
dominant polycystic kidney disease (ADPKD) is the fourth most
common cause for renal transplantation and is responsible for up to
10% of end-stage renal disease. [1] Mutations in the PKD1 and PKD2
genes result in ADPKD. Autosomal-recessive polycystic kidney disease
(ARPKD) is childhood-onset polycystic kidney disease with the
incidence of 1 in 20,000 live births and is an important cause of
chronic kidney disease in children and is caused by mutations in
PKHD1 gene. [2]
In some renal disorders many genes can be involved in the
pathogenesis of a single pathologic entity. Focal segmental
glomerulosclerosis (FSGS) can be caused by mutations in more than 20
podocyte-specifc genes such as NPHS1, NPHS2, WT-1, LAMB2,
CD2AP, TRPC6, ACTN4 and INF2 [3]. In these conditions
clarifcation of genotype-phenotype relationships would be important
in targeted therapy and prognostication.
Renal disorders sometimes infuenced by genetic factors, however,
not with Mendelian pattern of inheritance. In these conditions, a renal
disorder can be a multi-factorial disorder or shows susceptibility due to
specifc genetic polymorphisms. Nephropathy resulted from diabetes
mellitus or hypertension is a multi-factorial disorder, that is, caused by
interaction of environmental factors with multiple genes or genetic
susceptibility that determine the time of onset and the rate of
progression of the renal disease. For example, a polymorphism in the
CNDP1 gene, which encodes the enzyme carnosinase-1, determines
susceptibility to develop diabetic nephropathy [4].
Renal disorders sometimes are part of genetic syndromes or
disorders with or without dysmorphic features. For example in
tyrosinemia type I which is associated with liver dysfunction and renal
tubular dysfunction, due to mutations in FAH gene [5], there is no
dysmorphism. On the other hand, there is constellation of dysmorphic
features associated with renal disorder in many genetic syndromes
such as branchio-oto-renal (BOR) syndrome. Dysmorphic features of
BOR syndrome include prominent ears, low-set ears, auricular pits and
tags associated with middle, and inner ear anomalies, branchial fstulae
and cysts. Renal malformations which may occur in BOR syndrome
include renal agenesis, multiple renal cysts, renal dysplasia, ectopic
kidneys, hydronephrosis, small kidneys, double ureters, urinary refux
and ureteral atresia. Mutations in three genes EYA1, SIX1, and SIX5
can result in BOR syndrome. [6]
In brief, the genetic predisposition factors have a crucial impact on
the renal diseases. Tese factors may be a monogenic condition leading
to a known renal disease, or a multi-factorial condition and
polymorphisms that determine time of onset and progression rate of a
renal disease. And sometimes a renal disorder is a component of a
genetic syndrome. Current advances in whole genome analysis can
reveal the role of genetic variants and polymorphisms in the
development of diferent kidney diseases.
References
1. Spithoven E, Kramer A, Meijer E, Orskov B, Wanner C, et al. (2014) Renal
replacement therapy for autosomal dominant polycystic kidney disease
(ADPKD) in Europe: Prevalence and survival-an analysis of data from the
ERA-EDTA Registry. Nephrol Dial Transplant 29: 15-25.
2. Adeva M, El-Youssef M, Rossetti S, Kamath PS, Kubly V, et al. (2006)
Clinical and molecular characterization defines a broadened spectrum of
autosomal recessive polycystic kidney disease (ARPKD). Medicine
(Baltimore) 85: 1-21.
3. Chen YM, Liapis H (2015) Focal segmental glomerulosclerosis: Molecular
genetics and targeted therapies. BMC Nephrol 16: 101.
4. Janssen B, Hohenadel D, Brinkkoetter P, Peters V, Rind N, et al. (2005)
Carnosine as a protective factor in diabetic nephropathy-association with a
leucine repeat of the carnosinase gene CNDP1. Diabetes 54: 2320-2327.
5. St-Louis M, Tanguay RM (1997) Mutations in the fumarylacetoacetate
hydrolase gene causing hereditary tyrosinemia type I: Overview. Hum
Mutat 9: 291-299.
6. Krug P, Morinière V, Marlin S, Koubi V, Gabriel HD, et al. (2011) Mutation
screening of the EYA1, SIX1 and SIX5 genes in a large cohort of patients
harboring branchio-oto-renal syndrome calls into question the pathogenic
role of SIX5 mutations. Hum Mutat 32: 183-190.
Rad, J Kidney 2017, 3:3
DOI: 10.4172/2472-1220.1000e109
Editorial Open Access
J Kidney, an open access journal
ISSN:2472-1220
Volume 3 • Issue 3 • 1000e109
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ISSN: 2472-1220
Journal of Kidney