Urotensin 2 and retinoic acid receptor alpha (RARA) gene expression in IgA nephropathy.
BACKGROUND
IgA nephropathy is a disease where the pathogenesis is still poorly understood. Deoxyribonucleic acid (DNA) microarray technique allows tens of thousands of gene expressions to be examined at the same time. Commercial availability of microarray genechips has made this powerful tool accessible for wider utilisation in the study of diseases.


METHODS
Seven patients with IgA nephropathy, 6 with minimal change nephrotic syndrome (MCNS) as patient controls and 7 normal healthy subjects were screened for the differential expression of genes, genome-wide. The Human Genome U133 Plus 2.0 Arrays (Affymetrix, USA) were used to quantitate the differential expression of 38,500 well-characterised human genes.


RESULTS
A total of 7761 gene expressions were identified that have an IgAN/Normal gene expression ratio of 0.06-fold to 5.58-fold. About 35% of the altered gene expressions have no gene title or just a hypothetical protein label such as FLJ30679. Most of the remaining 65% are identified proteins where their importance to IgAN is not immediately apparent at this time. Among the 30 most upregulated and 30 most downregulated genes are Urotensin 2 (upregulated 3.09-fold, P <0.05) and Fatty-acid binding protein 6 (downregulated to 0.12-fold, P <0.05). Retinoic acid receptor alpha (vitamin A receptor) was also found downregulated to 0.41-fold (P <0.005). Taqman realtime polymerase chain reaction (PCR) for urotensin 2 and retinoic acid receptor alpha (RARA) were performed on 20 patients with IgA nephropathy and 11 with Minimal Change Disease and the data correlated with various clinical indices.


CONCLUSIONS
The findings suggest that there may be a therapeutic role for retinoic acid receptor alpha (RARA) in IgA nephropathy and a clinical monitoring role for Urotensin 2 in Minimal Change Disease.
Department of Renal Medicine, Singapore General Hospital, Singapore. woo.keng.thye@sgh.com.sg
Keng Thye
KT
Woo
Yeow Kok
YK
Lau
Yi
Y
Zhao
Kim Yoong
KY
Puong
Hwee Boon
HB
Tan
Stephanie
S
Fook-Chong
Kok Seng
KS
Wong
Choong Meng
CM
Chan
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*
D007070:Immunoglobulin A; D043562:Receptors, G-Protein-Coupled; D018168:Receptors, Retinoic Acid; C121697:UTS2R protein, human; D014212:Tretinoin