Donor and Recipient Angiotensin II Type 1 Receptor Polymorphisms and Haplotypes and Allograft Outcome in Renal Transplantation.

Abstract

We investigated the association between single nucleotide polymorphisms and haplotypes of the Angiotensin II Type 1 receptor (AGTR1), and long term kidney allograft outcome. Three thousand adult, deceased donor kidney transplant recipients and paired donors (transplanted 1988 to 2010) were randomly selected from Caucasian recipient and donor pairs in the Collaborative Transplant Study DNA bank. DNA specimens were genotyped for 6 single nucleotide polymorphisms (SNPs) of the AGTR1. The selected polymorphisms were tag SNPs within the two haplotype blocks (1 and 2) of the AGTR1 gene (haplotype 1: rs2933249, rs10935724, rs4681443; haplotype 2: rs718858, rs1492099, rs12721331). The primary outcome was 10-year allograft survival (Kaplan-Meier survival censored for death). We analysed outcomes by individual recipient and donor genotypes and haplotypes (wild-type versus remainder) as well as groups (presence or absence of minor allele), according to the recipient and donor AGTR1 genotype and haplotype. The selected sample was representative of the DNA bank (recipient age ≥18 years, Caucasian recipient and donor and initially on a calcineurin inhibitor). The mean transplant year was 1996. 437 (15%) of recipients were retransplants. Overall, median (interquartile range) follow up time was 7.5 (3.3-13.0) years and the mean 10-year death censored graft survival rate was 69.5%. The recipient mean (standard deviation, SD) age was 48 (13) yrs with 38% female. The donor mean (SD) age was 41 (17) yrs with 40% female. There were no significant (p<0.05) associations between donor or recipient AGTR1 SNPs and recipient allograft outcome. Similarly, neither haplotype of the donor nor recipient was significantly associated with recipient allograft outcome. When grouping the donor and recipient for individual AGTR1 SNP (p=0.29-0.97) or haplotype (p=0.68, p=0.93), again there was no significant association with the primary outcome. These individual SNPs or haplotypes of the AGTR1, whether in the donor, recipient or any combination of donor-recipient, were not associated with 10-year allograft outcome in the recipient following deceased donor kidney transplantation.