Genetic Polymorphism of NAD(P)H:Quinine Oxidoreductase 1 Is Associated with An Increased Treatment-Related Mortality in Patients Undergoing Allogeneic Transplantation.

The widely expressed detoxification enzyme NAD(P)H:quinine oxidoreductase 1 (NQO1) is involved in the cellular response to oxidative stress and irradiation and protects cells against the mutagenicity from free radicals and toxic oxygen metabolities. NQO1 is subject to a genetic polymorphism (C609T) leading to a change in its amino acid sequence. Heterozygous individuals C/T have intermediate activity and homozygotes T/T are NQO1 deficient. Never before the influence of genetic polymorphisms of NQO1 on patients who underwent allogeneic transplantation, was evaluated.

Here we genotyped in a retrospective study 198 patients (and their donors) for NQO1 expression that underwent allogeneic transplantation for various diseases and analyzed their outcome. Genotyping of NQO1 was performed by real-time PCR using subsequent melting curve analysis.

145 patients (73.2%) were genotyped as homozygous wild-type gene C/C, 48 patients (24.2%) were genotyped as heterozygous genotype C/T and five patients (2.5%) were genotype as homozygous gene mutation T/T. From the donors 147 donors (74.2%) were C/C, 50 donors (25.3%) were C/T, and one donor (0.5%) had a homozygous gene mutation T/T. Calculated genotype frequencies did not differ from that reported earlier by other studies for Caucasians. Five-year estimate for treatment-related mortality (TRM) was highest in genotype C/T- and T/T-patients with 39% ±11% compared to homozygous wild-type gene C/C-patients (21% ± 3.9% [p<0.045]), whereas the five-year estimate for relapse or overall survival (OS) were not statistically different between the groups. No differences for five-year estimates for TRM, relapse rate, or OS were seen in recipients with either genotype C/C-, C/T- or T/T-donors. No statistic differences were found in the incidence of acute GVHD grade 2-4 within the study groups. NQO1 C/T, T/T genotypes were not associated with elevated bilirubin or creatinin levels regarding on recipient or the donor side, even after stratification based on HLA disparity.

These results suggest that patients with genetic polymorphism of NQO1 do have an increased TRM after transplantation. Genotyping for NQO1 (C609T) might help to identify patients with higher risk for TRM.

No relevant conflicts of interest to declare.