Predisposition towards urolithiasis associated with the NQO1 null-allele.
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.
Schulz
W A
WA
Institut für Physiologische Chemie I, Düsseldorf, Germany.
Krummeck
A
A
Rösinger
I
I
Schmitz-Dräger
B J
BJ
Sies
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002135:Calcium-Binding Proteins; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D014545:Urinary Calculi / Q000209:etiology / Q000235:genetics*
D002135:Calcium-Binding Proteins; D016660:NAD(P)H Dehydrogenase (Quinone)