Familial calcium stone disease:: TaqI polymorphism and the vitamin D receptor

Background and Objective: Calcium nephrolithiasis has a strong familial component. However, to date, no specific genetic abnormality has been identified. Allelic variation in the vitamin D receptor (VDR) gene has been suggested as a partial explanation of differential calcium absorption or excretion in these patients. Polymorphism of this gene has been associated with altered vitamin D activity and has been implicated in osteoporosis and prostate cancer, We propose that a similar association may be found between familial hypercalciuric stone disease and the VDR, Subjects and Methods: Genomic DNA was isolated from 37 controls and 19 patients with hypercalciuria (>250 mg/24 hours) and a family history of nephrolithiasis, A 740-basepair segment of the VDR gene was amplified by polymerase chain reaction, digested with TaqI endonuclease, and resolved by gel electrophoresis. Alleles were classified as "T" if only one TaqI site was present and "t" if two were present. A simplified strength of family history score (FHS) was computed by adding 2 and 1 points, respectively, for each first- and second-degree relative affected by stone disease, Results: No difference in allelic or genotypic frequencies between the study and control groups was present, In the stone group, a significant association was found between the strength of the family history and the TI genotype, Patients with this genotype had an average FHS of 4.0, whereas the mean FHS for the Tt and tt genotypes was 2.0 and 1.8, respectively (P < 0.05), Nonsignificant trends of the TT genotype toward a higher number of stone episodes (19 v 13 and 3) and higher 24-hour urine calcium excretion (408 v 297 and 353 mg) were also noted in the study group, Conclusion: The results suggest that the TT genotype is associated with more aggressive stone disease, both within families and with respect to recurrence. Quantifying the risk of calcium stone disease through DNA markers has potential application in determining the risk of a patient's family members for nephrolithiasis or a patient's risk of recurrence, This information may have therapeutic implications with regard to the rigor of medical therapy and frequency of follow-up.