Faculty Collaboration Database

Evidence of gene-gene interactions in the genetic susceptibility to renal impairment after unilateral nephrectomy. J Am Soc Nephrol 2000 Nov;11(11):2068-2078

Date

10/29/2000

Pubmed ID

11053483

DOI

10.1681/ASN.V11112068

Scopus ID

2-s2.0-0033760910 (requires institutional sign-in at Scopus site)   66 Citations

Abstract

The number of patients with hypertension-associated end-stage renal failure (ESRF) continues to increase despite improved antihypertensive management and early detection programs. Variation for the development of renal complications in hypertension may reflect independent genetic susceptibility to ESRF. The genetically hypertensive fawn-hooded rat is characterized by the early presence of systolic hypertension, glomerular hypertension, progressive proteinuria (UPV), and focal glomerulosclerosis (FGS), resulting in premature death as a result of renal failure. In the present study, the genetic basis of hypertension-associated ESRF in an F2 intercross consisting of 337 animals, in which systolic BP, UPV, albuminuria, and FGS, were studied at 8 wk after a unilateral nephrectomy performed at 5 to 6 wk of age. A total genome scan, consisting of 418 markers, was used to identify regions that contribute to the pathogenesis of UPV and FGS. Linkage analysis revealed five loci involved in the development of renal impairment. Of these five, two (Rf-1, Rf-2) had been identified previously. There seems to be strong interactive effects between the various loci and their impact on UPV and the other parameters of renal impairment, as well as an interaction with BP. In particular, Rf-1 seems to play a major role in determining the severity of the disease. This study is the first to report the interaction of more than two loci to produce progressive renal failure, suggesting that the genetic dissection of renal failure in humans will require understanding of how multiple genes interact with each other and BP to produce ESRF.

Author List

Shiozawa M, Provoost AP, Dokkum RPEV, Majewski RR, Jacob HJ

MESH terms used to index this publication - Major topics in bold

Animals
Chromosome Mapping
Genetic Predisposition to Disease
Humans
Kidney Diseases
Nephrectomy
Quantitative Trait, Heritable
Rats
Rats, Inbred ACI
Rats, Inbred Strains
Sequence Homology
Species Specificity