A Polymorphism of the ORAI1 Gene is Associated With the Risk and Recurrence of Calcium Nephrolithiasis

Purpose: Store-operated calcium entry has been considered an important factor to regulate inflammatory reactions in nonexcitable cells. However, the effects of genetic polymorphisms of ORAI1, a main component of store-operated calcium channels, on nephrolithiasis and stone recurrence remain unclear. We investigated the association between calcium containing nephrolithiasis and genetic variants of ORAI1 gene in Taiwanese patients. Materials and Methods: A case-control study was performed in 136 patients with nephrolithiasis and 500 controls. Five tagging single nucleotide polymorphisms of ORAI1 were selected for genotyping. ORAI1 genotypes were determined by TaqMan (R) assay. Hardy-Weinberg equilibrium in cases and controls was assessed, and genetic effects were evaluated by the chi-square test and sliding window haplotype analysis. Subset analysis was done according to family history. Results: Two single nucleotide polymorphisms (rs12313273 and rs6486795) of the ORAI1 gene were associated with the risk of nephrolithiasis. The C allele carrier for rs12313273 was strongly related to recurrent stone forming in patients. On sliding window analysis the results of the 2 (rs12313273 and rs7135617) and the 3 (rs12313273, rs7135617 and rs6486795) single nucleotide polymorphism haplotypes had more significant effects on the risk of nephrolithiasis than the single nucleotide polymorphism rs12313273. Conclusions: To our knowledge this is the first study identifying the novel polymorphisms of the ORAI1 gene, which may predispose to the risk of calcium nephrolithiasis and disease recurrence.