[Role of transforming growth factor beta-1 gene polymorphisms in the development of chronic allograft nephropathy in renal transplant recipients].
BACKGROUND
Chronic allograft nephropathy (CAN) is the main cause of graft loss after the first year of transplantation, and renal biopsies show a predominance of fibrotic lesions. Human transforming growth factor beta-1 (TGF-beta 1) is the principal profibrogenetic cytokine which has been recently implicated in the development of CAN. Seven TGF-beta 1 gene polymorphisms have been recently described and some of them have been related to the development of several diseases.


OBJECTIVE
To analyse the relationship between TGF-beta 1 gene polymorphisms and the development of CAN in a group of renal transplant patients with a long-term follow-up.


METHODS
A restriction enzyme-based method for TGF-beta 1 genotyping was used to detect four TGF-beta 1 gene polymorphisms in codon 10, 25 and 5'-flanking region (-800 and -509 positions). A retrospective case-control study were performed on sixty renal transplant recipients with 8 years of post-transplant, 22 of them with CAN (cases) and 38 with normal graft function (controls). We studied 73 subjects to analyse the distribution of the genotypes in the area.


RESULTS
The genotype frequencies were similar in the study and control group. The presence of chronic allograft nephropathy was statistically associated with the combination Pro/Pro10 TT509 polymorphism in the TGF-beta 1 gene, and these patients develop chronic rejection more quickly than the rest of the patients. Chronic allograft nephropathy was also associated with delta age recipient-donor, with older donors being a significant risk factor for chronic nephropathy. The logistic regression analysis confirmed the independent role of TT509 Pro/Pro10 TGF-beta 1 polymorphism with a Odd Ratio of 5.8 (1.14-29.7) in chronic nephropathy being the delta age recipient-donor a confounder factor but not an effect modifier. The rest of the TGF-beta 1 gene polymorphisms and the classic risk factors were not associated with the development of chronic allograft nephropathy.


CONCLUSIONS
These data suggest a leading role for TGF-beta 1 gene polymorphisms (TT509 Pro/Pro10) in the development of chronic allograft nephropathy. The identification of this genetic predisposition to chronic allograft rejection could play a decisive role in the prevention of this common pathology.
Iñigo
P
P
Servicio de Nefrología del Hospital Clínico de Zaragoza. pinigo@comz.org
Lario
S
S
Campistol
J M
JM
Bescós
M
M
Campos
B
B
Oppenheimer
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D014184:Transplantation, Homologous
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1