Division of Nephrology, Tufts Medical Center, Boston, Mass., USA.
Nephron Clin Pract. 2010;114(4):c253-9. doi: 10.1159/000276577. Epub 2010 Jan 20.
BACKGROUND/AIMS: The catecholaminergic pathway is important in the physical stress response; however, its role is not well understood in acute kidney injury (AKI). We studied single nucleotide polymorphisms (SNPs) of phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme of the catecholaminergic pathway, and their association with adverse outcomes in AKI.
We performed a case-control study of 961 Caucasian subjects (194 with AKI and 767 controls). The PNMT promoter G-161A (rs876493) and coding A+1543G (rs5638) SNPs were genotyped and haplotypes generated. The outcomes of interest were the development of AKI, in-hospital mortality, dialysis requirement, oliguria, and hemodynamic shock. Urine catecholamines were measured in cases to explore genotype-phenotype correlations.
The PNMT +1543 G allele was associated with AKI [odds ratio (OR) 2.19, 95% confidence interval (CI): 1.04-4.60]. For AKI cases, each PNMT -161 A allele was associated with lower mortality (OR 0.58, 95% CI: 0.35-0.99) and hemodynamic shock (OR 0.63, 95% CI: 0.40-1.00). The PNMT +1543 G allele was associated with oliguria (OR 3.35, 95% CI: 1.13-9.95). Urine adrenaline was associated with increased hemodynamic shock and mortality, but was lowest in PNMT -161 A/A carriers.
In Caucasians, PNMT SNPs are associated with the development of AKI, disease severity, and in-hospital mortality. The adrenergic pathway provides another area of focus in the study of AKI.
背景/目的：儿茶酚胺能通路在身体应激反应中很重要；然而，其在急性肾损伤（AKI）中的作用还不是很清楚。我们研究了儿茶酚胺能通路末端酶苯乙醇胺 N-甲基转移酶（PNMT）的单核苷酸多态性（SNP）及其与 AKI 不良结局的关联。
我们对 961 名白种人受试者（194 名 AKI 患者和 767 名对照者）进行了病例对照研究。PNMT 启动子 G-161A（rs876493）和编码 A+1543G（rs5638）SNP 进行了基因分型，并生成了单体型。感兴趣的结局是 AKI 的发生、住院死亡率、透析需求、少尿和血流动力学休克。为了探索基因型-表型相关性，对病例组进行了尿儿茶酚胺的测量。
PNMT+1543 G 等位基因与 AKI 相关[比值比（OR）2.19，95%置信区间（CI）：1.04-4.60]。对于 AKI 患者，每个 PNMT-161 A 等位基因与较低的死亡率（OR 0.58，95% CI：0.35-0.99）和血流动力学休克（OR 0.63，95% CI：0.40-1.00）相关。PNMT+1543 G 等位基因与少尿相关（OR 3.35，95% CI：1.13-9.95）。尿肾上腺素与血流动力学休克和死亡率的增加相关，但在 PNMT-161 A/A 携带者中最低。
在白种人中，PNMT SNP 与 AKI 的发生、疾病严重程度和住院死亡率相关。儿茶酚胺能通路为 AKI 的研究提供了另一个关注领域。
