Microarray analysis of focal segmental glomerulosclerosis.
BACKGROUND
Focal segmental glomerulosclerosis (FSGS) is a leading cause of chronic renal failure in children. Recent studies have begun to define the molecular pathogenesis of this heterogeneous condition. Here we use oligonucleotide microarrays to obtain a global gene expression profile of kidney biopsy specimens from patients with FSGS in order to better understand the pathogenesis of this disease.


METHODS
We extracted RNA from renal biopsy samples of 10 patients with the diagnosis of FSGS and from 5 control kidney samples, and produced labeled cRNA for hybridization to Affymetrix human U133A microarrays.


RESULTS
We identified a gene expression fingerprint for FSGS that contained 429 of 22,283 possible genes, each with a p < 0.01, using RMA normalization, Welch t test, and at least a 1.8-fold change in 5 of the 10 patients examined. We also found gene expression differences in samples from subsets of patients who had either nephrotic syndrome or renal insufficiency. This screen identified many genes and genetic pathways that have already been implicated in the pathogenesis of FSGS. In addition, we found changes in gene expression in genetic pathways that have not been studied in FSGS.


CONCLUSIONS
Oligonucleotide DNA microarray analysis of renal biopsy specimens identified a gene expression fingerprint in samples from a heterogeneous population of patients with FSGS. The genes and genetic pathways identified in this study can be compared to results of similar studies of other diseases to examine specificity and used to study the pathogenesis of FSGS.
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Kristopher
K
Schwab
David P
DP
Witte
Bruce J
BJ
Aronow
Prasad
P
Devarajan
S Steven
SS
Potter
Larry T
LT
Patterson
D000293:Adolescent; D000941:Antigens / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics; D015536:Down-Regulation; D005136:Eye Proteins; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D007473:Ion Channels / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D009404:Nephrotic Syndrome / Q000235:genetics* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D018078:Receptors, Prostaglandin E / Q000235:genetics; D058308:Receptors, Prostaglandin E, EP3 Subtype; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation
D000941:Antigens; C486602:CHRDL1 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; C406887:IFI27 protein, human; C065888:IFI44 protein, human; D007473:Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C545647:PTGER3 protein, human; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D014157:Transcription Factors