Cytokine single nucleotide polymorphisms and intrarenal gene expression in chronic allograft nephropathy in children.
BACKGROUND
Single nucleotide polymorphisms (SNPs) have been reported to influence cytokine production. Certain cytokine high producer genotypes have been associated with an increased risk for acute rejection and chronic allograft dysfunction (CAD) after transplantation. Our study evaluates SNP distribution for transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha) in pediatric renal transplant recipients and control individuals and correlates them to corresponding intrarenal gene expression.


METHODS
SNPs for TGF-beta1 (codon 10 and 25), IL-10 (positions -1082, -819, -592) and TNF-alpha (position -308) were determined in 30 patients with stable graft function, in 75 patients with CAD, and in 173 control individuals by allele-specific polymerase chain reaction (PCR). Intrarenal cytokine gene expression was studied in 25 biopsies with chronic allograft nephropathy (CAN) and 27 normal kidney specimens by real-time reverse transcription (RT)-PCR.


RESULTS
No difference in allele and genotype frequency was detected in any of the investigated groups. No correlation between genotype and intragraft cytokine gene expression was recognized in CAN patients. However, in normal kidney specimens, the low producer TGF-beta1 genotype at codon 10 was associated with significant lower TGF-beta1 mRNA expression. This association was not found for IL-10 or TNF-alpha.


CONCLUSIONS
Our results do not support the proposition that certain specific cytokine genotypes for TGF-beta1, IL-10, and TNF-alpha are associated with CAD. Intrarenal cytokine gene expression only correlated to one TGF-beta1 SNP in normal kidney specimens. Since overall TGF-beta1 expression was higher in transplanted patients compared to controls, this suggests that SNPs may not play a significant role once the immune system is activated.
Melk
Anette
A
Childrens' Hospital, Hannover Medical School, Hannover, Germany. anettemelk@yahoo.de
Henne
Thomas
T
Kollmar
Thorsten
T
Strehlau
Jürgen
J
Latta
Kay
K
Offner
Gisela
G
Jhangri
Gian S
GS
Ehrich
Jochen H H
JH
Von Schnakenburg
Christian
C
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006085:Graft Survival / Q000235:genetics; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000209:etiology* / Q000235:genetics*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10