Phenylethanolamine N-Methyltransferase Gene Polymorphisms and Adverse Outcomes in Acute Kidney Injury

Abstract

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. Methods: 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. Results: 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. Conclusion: 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.