Association of hypertension genotypes and decline in renal function after kidney transplantation
Association of hypertension genotypes and decline in renal function after kidney transplantation
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DOI：
10.1097/01.tp.0000287324.95119.ae
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发表时间：
2007-11-27
期刊：
影响因子：
6.2
通讯作者：
Feldman, Harold I.
中科院分区：
文献类型：
--
作者：
Israni, Ajay K.;Li, Na;Feldman, Harold I.
背景。血管紧张素转换酶 (ACE)、血管紧张素原 (AGT) 和 I 型血管紧张素受体 (AGTR1) 等基因的多态性与高血压有关。反过来，高血压又与肾同种异体移植物存活率降低有关。因此，本研究调查了这些基因中的单核苷酸多态性（SNP）是否与移植后肾功能下降有关。方法。我们从特拉华谷地区 9 个中心进行的已故捐献肾脏前瞻性肾移植受者队列中招募了患者。每 6 个月评估一次医疗记录，并使用肾病饮食修改方程计算估计肾小球滤过率 (eGFR)。分别分析AGTR1、AGT和ACE基因中10、2和5个SNP的基因型。结果。 AGTR1 SNP rs275704 和 rs5182 各自的 G 和 T 等位基因均与 eGFR 下降 50% 相关（rs275704 的 HR：CG= 1.22，95% 置信区间 [CI] 0.67-2.25 和 GG=2.55，95% Cl 1.22-5.32，总体 P=0.03；HR rs5182：CT= 1.26,95% Cl 0.72-2.19 和 TT=3.09,95% Cl 1.50-6.37，总体 P=0.007）在调整分析中。同样，单倍型分析显示 AGTR1 SNP 与 eGFR 下降 50% 相关（总体 P=0.010）。 SNP rs275704 出现 GG 基因型。非裔美国人比非非裔美国人更常见（44% vs. 7%，chi(2)=36.03，P
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% Cl 1.22-5.32, overall P=0.03; HR for rs5182: CT= 1.26,95% Cl 0.72-2.19 and TT=3.09,95% Cl 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%, chi(2)=36.03, P