Relationship between subclinical rejection and genotype, renal messenger RNA, and plasma protein transforming growth factor-beta1 levels.
BACKGROUND
Transforming growth factor (TGF)-beta(1) is increased in allograft rejection and its production is associated with single nucleotide polymorphisms (SNPs).


METHODS
The contribution of SNPs at codons 10 and 25 of the TGF-beta(1) gene to renal allograft damage was assessed in 6-month protocol biopsies and their association with TGF-beta(1) production. TGF-beta(1) genotypes were evaluated by polymerase chain reaction (PCR)/restriction fragment length polymorphism. Intragraft TGF-beta(1) messenger RNA (mRNA) was measured by real-time PCR and TGF-beta(1) plasma levels were assessed by enzyme-linked immunosorbent assay.


RESULTS
Eighty consecutive patients were included. Allele T at codon 10 (risk ratio, 6.7; P = 0.02) and an episode of acute rejection before protocol biopsy (risk ratio, 6.2; P = 0.01) were independent predictors of subclinical rejection (SCR). TGF-beta(1) plasma levels, but not those of TGF-beta(1) mRNA, were increased in patients with SCR (2.59 ng/mL +/- 0.91 [n = 22] vs. 2.05 ng/mL +/- 0.76 [n = 43]; P = 0.01). There was no association between allele T and TGF-beta(1) plasma or intragraft levels.


CONCLUSIONS
Allele T at codon 10 of the TGF-beta(1) gene is associated with a higher incidence of SCR.
Hueso
Miguel
M
IDIBELL, Department of Nephrology, Hospital Universitario Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Navarro
Estanis
E
Moreso
Francesc
F
Beltrán-Sastre
Violeta
V
Ventura
Francesc
F
Grinyó
Josep M
JM
Serón
Daniel
D
D000328:Adult; D001706:Biopsy; D002985:Clinical Protocols; D005260:Female; D005838:Genotype; D006789:Host vs Graft Reaction / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta