PREDISPOSITION TOWARDS UROLITHIASIS ASSOCIATED WITH THE NQ01 NULL-ALLELE

The distribution of two alleles of the NQO1 gene encoding NADP(H):quin one oxidoreductase was studied in 140 urolithiasis patients and 271 co ntrol 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 i ncreased risk for kidney stone formation among heterozygotes (odds rat io 1.83, confidence interval 1.17-2.86) and homozygotes for the null-a llele (odds ratio 2.97, confidence interval 0.78-11.33). Since NADP(H) :quinone oxidoreductase is thought to participate in activation of vit amin It for protein gamma-carboxylation, decreased activity of the enz yme in heterozygotes or in null-allele homozygotes may disturb the pos t-translational modification of urinary calcium-binding proteins prote ctive against kidney stone formation, The NQO1 null-allele might there fore be a determinant in enhanced risk of urolithiasis. Pharmacogeneti cs 8:453-454 (C) 1998 Lippincott Williams & Wilkins.