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

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

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).

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. We excluded the CaR (lod score <-2) at lambdas values of 1.5, 1.68, and 2.6 for sib pairs concordant for at least one stone passage, at least two stone passages, and at least one stone passage and calciuria above the 75th percentile, respectively. Quantitative trait linkage analyses did not suggest that the CaR gene was linked to biochemical markers of idiopathic hypercalciuria.

This study shows that genetic variants of the CaR gene are not associated with idiopathic hypercalciuria and calcium nephrolithiasis in this population of French Canadians.