Predisposition towards urolithiasis associated with the NQ01 null-allele

Schulz, Wolfgang A.; Krummeck, Angelika; Rösinger, Ingrid; Schmitz‐Dräger, Bernd J.; Sies, Helmut

doi:10.1097/00008571-199810000-00011

Cited by 16 publications

(6 citation statements)

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“…Individuals carrying both mutated genomic alleles are completely deficient in NQO1 activity, whereas heterozygous individuals have intermediate NQO1 activity compared with normal individuals [29,30]. Approximately 2–4% individuals are homozygous and 20–25% are heterozygous for this mutation [31,32]. The current studies suggest that human individuals that carry NQO1P187S homo- or heterozygous mutation are susceptible to develop PBS and are a subject of future investigation.…”

Section: Discussionmentioning

confidence: 96%

NAD(P)H:quinone oxidoreductase 1 protects bladder epithelium against painful bladder syndrome in mice

Patrick¹,

Das²,

Jaiswal³

2012

Free Radical Biology and Medicine

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Painful Bladder Syndrome (PBS) or interstitial cystitis (IC) is a poorly understood chronic disease, which is characterized by thinning of bladder epithelium and intense pain. Here we demonstrate that NAD(P)H:quinone oxidoreductase 1−/− (NQO1−/−) mice developed in our laboratory represent a new animal model of PBS. NQO1 is known to protect against physiological stress as well as transcription factors against proteasomal degradation. In the present study we demonstrate that NQO1 is necessary for bladder epithelium integrity, and to prevent the development/progression of PBS. We observed down regulation of energy metabolism, adhesion, and apoptotic signaling cascades, which led to mitochondrial aberrations and profound alterations in energy metabolism, increased susceptibility to ROS generation and apoptosis in luminal epithelium in NQO1−/− mice that were absent in wild-type mice. These pathophysiological changes led to incidence of PBS in NQO1−/− mice. The results together demonstrate for the first time that NQO1 is an endogenous factor in protection against PBS.

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Section: Discussionmentioning

confidence: 96%

NAD(P)H:quinone oxidoreductase 1 protects bladder epithelium against painful bladder syndrome in mice

Patrick¹,

Das²,

Jaiswal³

2012

Free Radical Biology and Medicine

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“…NQO1*2 homozygosity appears to be correlated with an increased risk of renal cell cancer and urothelial cell carcinoma (Table 3), with OR values of 1.7 and 3.6, respectively 36 ; there is also a heightened predisposition toward urolithiasis (kidney stones) with an OR of 2.97. 37 For patients with renal cell carcinoma and urothelial carcinoma, 36 all 95% confidence intervals in this study contained the value of 1.0, however, except for the renal cell carcinoma NQO1*1/*2 heterozygotes compared with controls (Table 3). Again, a loss in power is likely due to the small study population (renal cell carcinoma patients, N ϭ 131; urothelial carcinoma patients, N ϭ 99; and controls, N ϭ 260).…”

Section: Interactions Nqo1*2 Allele and Other Diseasesmentioning

confidence: 57%

“…The distribution of the NQO1*2 allele in urolithiasis patient populations 37 was significantly higher, based on Mantel-Haenzel chi-squared analysis (P ϭ 0.003). Heterozygotes experienced a 1.8-fold increased risk of urolithiasis (95% CI, 1.17-2.86).…”

Section: Interactions Nqo1*2 Allele and Other Diseasesmentioning

confidence: 98%

NAD(P)H:quinone oxidoreductase (NQO1) polymorphism, exposure to benzene, and predisposition to disease: A HuGE review

Nebert

Roe²,

Vandale

et al. 2002

Genetics in Medicine

169

130

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“…A single nucleotide polymorphism (SNP) C to T at position 609 (rs1800566) in the NQO1 coding region (replacing proline with serine at codon 187) leads to lower enzyme activity and has been shown to be associated with increased risk of myeloid leukemia and bladder carcinoma[12,13]. Myeloperoxidase ( MPO ) is an endogenous oxidant enzyme that generates reactive oxygen species (ROS).…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphisms of CYP2E1, GSTP1, NQO1 and MPO and the Risk of Nasopharyngeal Carcinoma in a Han Chinese Population of Southern China

Guo

Zeng²,

Deng

et al. 2010

BMC Res Notes

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BackgroundSouthern China is a major area for endemic nasopharyngeal carcinoma (NPC). Genetic factors as well as environmental factors play a role in development of NPC. To investigate the roles of previously described carcinogen metabolism gene variants for NPC susceptibility in a Han Chinese population, we conducted a case-control study in two independent study population groups afflicted with NPC in Guangdong and Guangxi Provinces of southern China.MethodsFive single nucleotide polymorphisms (SNPs) of CYP2E1-rs2031920, CYP2E1-rs6413432, GSTP1-rs947894, MPO-rs2333227 and NQO1-rs1800566 were genotyped by PCR-based RFLP, sequencing and TaqMan assay in 358 NPC cases and 629 controls (phase I cohort). Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). To confirm our results, sixteen tag SNPs for GSTP1, MPO, NQO1 (which 100% covered these genes), and 4 functional SNPs of CYP2E1 were genotyped in another cohort of 213 NPC cases and 230 controls (phase II cohort).ResultsNo significant associations in NPC risk were observed for the five polymorphisms tested in the phase I cohort. In an additional stratified analysis for phase I, there was no significant association between cases and controls in NPC high risk population (EBV/IgA/VCA positive population). Analysis of 14 tagging SNPs within the same genes in an independent phase II cohort were in agreement with no SNPs significantly associated with NPC.ConclusionsOur results suggest that polymorphism of CYP2E1, GSTP1, MPO and NQO1 genes does not contribute to overall NPC risk in a Han Chinese in southern China.

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Predisposition towards urolithiasis associated with the NQ01 null-allele

Cited by 16 publications

References 0 publications

NAD(P)H:quinone oxidoreductase 1 protects bladder epithelium against painful bladder syndrome in mice

NAD(P)H:quinone oxidoreductase 1 protects bladder epithelium against painful bladder syndrome in mice

NAD(P)H:quinone oxidoreductase (NQO1) polymorphism, exposure to benzene, and predisposition to disease: A HuGE review

Genetic Polymorphisms of CYP2E1, GSTP1, NQO1 and MPO and the Risk of Nasopharyngeal Carcinoma in a Han Chinese Population of Southern China

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