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 sto nes. 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 chrom osome 12q12-14 is implicated in idiopathic hypercalciuria and calcium nephr olithiasis in a cohort of 47 French Canadian pedigrees. These comprised 54 sibships with a total of 303 pairs of siblings concordant for greater than or equal to 1 stone episode. Evidence is provided for linkage to nephrolith iasis with microsatellite marker D12S339 (near the VDR locus, P = 0.01), as well as with flanking markers (D12S1663: P = 0.03 and D12S368: P = 0.01). Inclusion of unaffected sibs in the analyses also supported evidence for li nkage. Quantitative trait linkage analysis of urinary calcium excretion yie lded linkage to some, but not all, markers. This appears to be the first st udy to suggest linkage for idiopathic calcium stone formation.