RESUMO
The distribution of two alleles of the NQO1 gene encoding NADP(H):quinone oxidoreductase was studied in 140 urolithiasis patients and 271 control individuals. The minor allele encoding a protein lacking quinone reductase activity was significantly more frequent (q = 0.214) among these patients than in control individuals (P = 0.135) indicating an increased risk for kidney stone formation among heterozygotes (odds ratio 1.83, confidence interval 1.17-2.86) and homozygotes for the null-allele (odds ratio 2.97, confidence interval 0.78-11.33). Since NADP(H):quinone oxidoreductase is thought to participate in activation of vitamin K for protein gamma-carboxylation, decreased activity of the enzyme in heterozygotes or in null-allele homozygotes may disturb the post-translational modification of urinary calcium-binding proteins protective against kidney stone formation. The NQO1 null-allele might therefore be a determinant in enhanced risk of urolithiasis.
Assuntos
NAD(P)H Desidrogenase (Quinona)/genética , Cálculos Urinários/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Proteínas de Ligação ao Cálcio , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Processamento de Proteína Pós-Traducional , Cálculos Urinários/etiologiaRESUMO
The NQO1 locus on chromosome 16q2.2 encodes NAD(P)H:quinone oxidoreductase, an enzyme implicated in detoxication and protection against redox cycling. Two alleles have been identified in the human population, the rarer one, termed the null-allele, coding for a nonfunctional enzyme. Since lack of NQOR activity has been suggested to increase susceptibility to certain cancers, the distribution of the two alleles was determined by polymerase chain reaction-restriction fragment length polymorphism analysis in patients with renal cell carcinoma (n = 131) and urothelial carcinoma (n = 99) compared with a normal population (n = 260). Allele distribution in the normal population followed a Hardy-Weinberg distribution with frequencies of 0.867 for the major allele and 0.133 for the null-allele. Increased frequencies of the null-allele were found in the tumour patient groups (0.191 and 0.182, respectively) due to an increased number of both homo- and heterozygotes. The odds ratios for homozygous null-allele vs. wild-type genotypes were 1.7 and 3.6 for renal cell carcinoma and urothelial carcinoma, respectively. These data are compatible with the assumption that diminished activity of NQOR in some individuals increases susceptibility to certain cancers.
