Transforming growth factor beta1 genotype polymorphisms determine AV fistula patency in hemodialysis patients.
BACKGROUND
In hemodialysis patients with an arteriovenous (AV) fistula, access failure is primarily due to fistula stenosis, which predisposes to thrombosis and subsequent access loss. The risk for access failure differs interindividually, an observation that is independent from vascular anatomy in a significant number of patients. Fistula stenosis is histologically characterized by intimal hyperplasia, which is induced by growth factors, among which transforming growth factor beta1 (TGF-beta1) is of major importance. The quantitative production of TGF-beta1 interindividually differs due to polymorphisms in the gene region encoding the signal sequence of the cytokine. We hypothesized that the TGF-beta1 genotype, by influencing the development of arteriovenous fistula stenosis, determines the risk for vascular access failure.


METHODS
One hundred twenty patients who had undergone placement of an AV fistula for initiation of hemodialysis treatment were genotyped for the polymorphic bases at position +869 and +915 of the TGF-beta1 gene. The primary end-point was time from fistula placement to access failure.


RESULTS
AV fistula patency was significantly associated with the TGF-beta1 genotype (P = 0.0046); patency was 62.4% and 81.2% after 12 months for TGF-beta1 high and intermediate producers, respectively. In contrast, AV fistula patency neither differed between diabetic and nondiabetic patients, nor between patients with and without manifest cardiovascular disease.


CONCLUSIONS
Polymorphisms in the gene region encoding the signal sequence of TGF-beta1 influence the risk for hemodialysis access failure. By inducing synthesis of extracellular matrix proteins, overproduction of TGF-beta1 may accelerate the development of intimal hyperplasia, resulting in fistula stenosis and subsequent access failure.
Heine
Gunnar H
GH
Medical Department IV, Nephrology, University Homburg, Homburg, Germany.
Ulrich
Christof
C
Sester
Urban
U
Sester
Martina
M
Köhler
Hans
H
Girndt
Matthias
M
D000368:Aged; D001166:Arteriovenous Shunt, Surgical; D003928:Diabetic Nephropathies / Q000150:complications; D005260:Female; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D006435:Renal Dialysis; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D014654:Vascular Patency
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1