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Association of hypertension genotypes and decline in renal function after kidney transplantation.

Israni AK, Li N, Sidhwani S, Rosas S, Kong X, Joffe M, Rebbeck T, Feldman HI

Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN 55415-1829, USA. isran001@umn.edu

BACKGROUND: Polymorphisms of genes such as angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and angiotensin receptor type I (AGTR1) have been associated with hypertension. Hypertension, in turn, has been associated with decreased renal allograft survival. Therefore, this study investigated whether single nucleotide polymorphisms (SNPs) in these genes are associated with decline in renal function posttransplantation. METHODS: We enrolled patients from a prospective cohort of renal transplant recipients of deceased donor kidneys being conducted at 9 centers in the Delaware Valley Region. Medical records were assessed every 6 months and estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation. Genotypes of 10, 2, and 5 SNPs in the AGTR1, AGT, and ACE gene were analyzed, respectively. RESULTS: The G and the T alleles of the respective AGTR1 SNPs rs275704 and rs5182 were both associated with 50% decline in eGFR (HR for rs275704: CG=1.22, 95% confidence interval [CI] 0.67-2.25 and GG=2.55, 95% CI 1.22-5.32, overall P=0.03; HR for rs5182: CT=1.26, 95% CI 0.72-2.19 and TT=3.09, 95% CI 1.50-6.37, overall P=0.007) in the adjusted analysis. Similarly, haplotype analysis showed that AGTR1 SNPs were associated with 50% decline in eGFR (global P=0.010). The GG genotype of SNP rs275704 occurred more frequently in African Americans than in non-African Americans (44% vs. 7%, chi2=36.03, P<0.0001). In contrast, the TT genotype of SNP rs5182 occurred more frequently in non-African Americans than in African-Americans (24% vs. 2%, chi2=21.40, P<0.0001). Polymorphisms in the ACE and AGT genes were not associated with renal allograft outcomes. CONCLUSIONS: SNPs in AGTR1 gene are associated with decline in renal function posttransplantation.

Published 30 November 2007 in Transplantation, 84(10): 1240-7.
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