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

Background. Calcium urolithiasis is in part genetically determined and asso ciated with idiopathic hypercalciuria. Methods. We have used a candidate gene approach to determine whether the ca lcium-sensing receptor (CaR) gene is linked to idiopathic hypercalciuria an d calcium urolithiasis in a cohort of French Canadian sibships with multipl e affected members (64 sibships from 55 pedigrees yielding 359 affected sib ling pairs with greater than or equal to 1 stone episode). Results. Using nonparametric linkage analysis with various intragenic and f lanking markers, we showed that the CaR gene could be excluded as a major g ene for hypercalciuric stone formation. We excluded the CaR (lod score <-2) at lambda s values of 1.5, 1.68, and 2.6 for sib pairs concordant for at l east one stone passage, at least two stone passages, and at least one stone passage and calciuria above the 75th percentile, respectively. Quantitativ e trait linkage analyses did not suggest that the CaR gene was linked to bi ochemical markers of idiopathic hypercalciuria. Conclusions. This study shows that genetic variants of the CaR gene are not associated with idiopathic hypercalciuria and calcium nephrolithiasis in t his population of French Canadians.