Angiotensin-converting enzyme genotype is a predictive factor in the peak panel-reactive antibody response.
The presence of a high panel-reactive antibody (PRA) level represents an independent risk factor for early graft failure and chronic allograft dysfunction. It has also been reported that patients with the ACE-DD and AGT-AA genotypes display poorer chronic allograft function. We investigated the effects of gene polymorphisms of the renin angiotensin system (RAS) on anti-HLA antibody production among renal transplant candidates. Genotyping was performed on 133 dialysis patients for the ACE (I/D) and AGT (M235T) as well as the type 1 (A1166C) and type 2 (A1223G) angiotensin II receptor genes. Patients with a peak PRA >/= 30% were considered to be positive for anti-HLA antibody (40.6% of 133 patients). Genetic polymorphisms of the RAS were not associated with anti-HLA antibody production at this PRA level. Another analysis comparing the 29 patients with a peak PRA >/=50% with the 104 patients with a peak PRA <50% showed that previous transplants, the presence of ACE-DD genotype, history of blood transfusions, and dialysis duration were all associated with the high levels of antibody production by univariant analysis. A multivariate analysis using a logistic regression model revealed previous transplants, the presence of ACE-DD genotype, and history of blood transfusions to be predictors of anti-HLA antibody production. The ACE-DD genotype is an important risk factor for higher PRA levels. This study suggests that genetic control of RAS activity correlates with production of anti-HLA antibodies, possibly explaining the relationship to chronic allograft outcome.
Akçay
A
A
Department of Nephrology, Baskent University Faculty of Medicine, Ankara, Turkey.
Ozdemir
F N
FN
Ataç
F B
FB
Sezer
S
S
Verdi
H
H
Arat
Z
Z
Haberal
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood*; D000917:Antibody Formation; D001323:Autoantibodies / Q000097:blood; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000097:blood; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D014850:Waiting Lists
D000906:Antibodies; D001323:Autoantibodies; D006680:HLA Antigens; D007703:Peptidyl-Dipeptidase A