Phenylethanolamine N-methyltransferase gene polymorphisms and adverse outcomes in acute kidney injury.
OBJECTIVE
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.


CONCLUSIONS
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.
Alam
Ahsan
A
Division of Nephrology, Tufts Medical Center, Boston, Mass., USA.
O'Connor
Daniel T
DT
Perianayagam
Mary C
MC
Kolyada
Alexey Y
AY
Chen
Yuqing
Y
Rao
Fangwen
F
Mahata
Manjula
M
Mahata
Sushil
S
Liangos
Orfeas
O
Jaber
Bertrand L
BL
D058186:Acute Kidney Injury / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006239:Haplotypes / Q000235:genetics; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D008297:Male; D008875:Middle Aged; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D006435:Renal Dialysis / Q000639:trends; D012720:Severity of Illness Index; D016896:Treatment Outcome
D010625:Phenylethanolamine N-Methyltransferase