Association of osteopontin gene haplotypes with nephrolithiasis

Osteopontin (OPN) is one of the glycosylated phosphoproteins produced in the kidney that can modulate nephrolithiasis. We had previously found a modest association between OPN gene polymorphisms and the risk for urinary stone formation. In order to determine if sequence variants within the OPN gene could be linked to the risk of nephrolithiasis; we sequenced the entire OPN gene of 45 stone forming patients and 54 control patients of Japanese ancestry. We identified 61 polymorphisms and of these evaluated four haplotype-tagging single nucleotide polymorphisms in a total of 126 kidney stone cases and 214 healthy individuals; all of Japanese ancestry. There was a significant association of two of these haplotypes located in the OPN promoter with the relative probability of nephrolithiasis; one of increased and one of reduced risk. Our findings provide potential support for significant increased and decreased associations between OPN gene haplotypes and the relative potential of stone formation in the Japanese population. We suggest that such genetic findings may help to clarify the function of OPN in nephrolithiasis.