Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An earlier linkage analysis conducted on a population derived from the Dahl salt-sensitive hypertensive (S) and the spontaneously hypertensive rat (SHR) identified 10 genomic regions linked to several renal and/or cardiovascular traits. In particular, loci on rat chromosomes (RNO) 8 and 13 were linked to proteinuria, albuminuria, and renal damage. At both loci, the S allele was associated with increased proteinuria and renal damage. The current study aimed to confirm the linkage analysis and to evaluate the effect of genetic background on the ability of each locus (either RNO8 or RNO13) to exert a phenotypic difference when placed on a genetic background either susceptible (S rat) or resistant (SHR) to the development of renal disease. Congenic strains developed to transfer genomic segments from either RNO8 or RNO13 from the SHR onto the S genetic background [S.SHR(8) or S.SHR(13)] demonstrated significantly reduced proteinuria and improved renal function. Both congenic strains demonstrated significantly reduced glomerular and tubular injury, with renal interstitial fibrosis as the predominant pathological difference compared with the S. In contrast, transfer of RNO8 or RNO13 genomic regions from the S onto the resistant SHR genetic background [SHR.S(8) or SHR.S(13)] yielded no significant difference in proteinuria or glomerular, tubular, or interstitial injury compared with SHR. These findings demonstrate that genetic context plays a significant and important role in the phenotypic expression of genes influencing proteinuria on RNO8 and RNO13.
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PMID:Investigating the effect of genetic background on proteinuria and renal injury using two hypertensive strains. 1917 3

Investigation of proteinuria, whose pathophysiology remains incompletely understood, is confounded by differences in the phenotype between males and females. We initiated a sex-specific geno-transcriptomic dissection of proteinuria in uninephrectomized male and female Sabra rats that spontaneously develop focal and segmental glomerulosclerosis, testing the hypothesis that different mechanisms might underlie the pathophysiology of proteinuria between the sexes. In the genomic arm, we scanned the genome of 136 male and 111 female uninephrectomized F2 populations derived from crosses between SBH/y and SBN/y. In males, we identified proteinuria-related quantitative trait loci (QTLs) on RNO2 and 20 and protective QTLs on RNO6 and 9. In females, we detected proteinuria-related QTLs on RNO11, 13, and 20. The only QTL overlap between the sexes was on RNO20. Using consomic strains, we confirmed the functional significance of this QTL in both sexes. In the transcriptomic arm, we searched on a genomewide scale for genes that were differentially expressed in kidneys of SBH/y and SBN/y with and without uninephrectomy. These studies identified within each sex differentially expressed genes of relevance to proteinuria. Integrating genomics with transcriptomics, we identified differentially expressed genes that mapped within the boundaries of the proteinuria-related QTLs, singling out 24 transcripts in males and 30 in females, only 4 of which (Tubb5, Ubd, Psmb8, and C2) were common to both sexes. Data mining revealed that these transcripts are involved in multiple molecular mechanisms, including immunity, inflammation, apoptosis, matrix deposition, and protease activity, with no single molecular pathway predominating in either sex. These results suggest that the pathophysiology of proteinuria is highly complex and that some of the underlying mechanisms are shared between the sexes, while others are sex specific and may account for the difference in the proteinuric phenotype between males and females.
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PMID:Geno-transcriptomic dissection of proteinuria in the uninephrectomized rat uncovers a molecular complexity with sexual dimorphism. 2087 44