Evaluation of the calcium-sensing receptor gene in idiopathic hypercalciuria and calcium nephrolithiasis.

Background: Calcium urolithiasis is in part genetically determined and associated with idiopathic hypercalciuria.

Methods: We have used a candidate gene approach to determine whether the calcium-sensing receptor (CaR) gene is linked to idiopathic hypercalciuria and calcium urolithiasis in a cohort of French Canadian sibships with multiple affected members (64 sibships from 55 pedigrees yielding 359 affected sibling pairs with > or =1 stone episode).

Results: Using nonparametric linkage analysis with various intragenic and flanking markers, we showed that the CaR gene could be excluded as a major gene for hypercalciuric stone formation.

Suggestive evidence for a susceptibility gene near the vitamin D receptor locus in idiopathic calcium stone formation.

Calcium is the principal crystalline constituent in up to 80% of kidney stones. Epidemiologic studies have suggested that genetic predisposition plays a major role in the etiology of this condition. This study evaluates by a candidate-gene approach whether the vitamin D receptor (VDR) locus on chromosome 12q12-14 is implicated in idiopathic hypercalciuria and calcium nephrolithiasis in a cohort of 47 French Canadian pedigrees.

The 1 alpha-hydroxylase locus is not linked to calcium stone formation or calciuric phenotypes in French-Canadian families.

Calcium urolithiasis is often associated with increased intestinal absorption and urine excretion of calcium, and has been suggested to result from increased vitamin D production. The role of the enzyme 1 alpha-hydroxylase, the rate-limiting step in active vitamin D production, was evaluated in 36 families, including 28 sibships with at least a pair of affected sibs, using qualitative and quantitative trait linkage analyses. Sibs with a verified calcium urolithiasis passage (n = 117) had higher 24-h calciuria (P = 0.