A family-based study investigating the genetic basis of calcium-containing kidney stones

There is strong evidence for a familial basis to renal stone disease. However, apart from a number of rare disorders for which the causative genetic mutations are known, our understanding of the heritability of renal stone disease is modest. To explore the familial basis of renal stone disease, the heritabilities of relevant biochemical trait were inspected and the possibility of renal stone linkage to a number of genetic loci was investigated.Families displaying a clustering of renal stone disease were recruited to the project. Data on the inheritance of renal stone disease within each pedigree was gathered. Biochemical parameters were evaluated in relation to the individual pedigrees in order to dissect traits that might predict risk of renal stone disease. A number of different parameters were discovered to have a strong predictive value for stone disease in individual families.A microsatellite-based approach to linkage analysis was developed. This approach was used to explore linkage between the renal stone forming trait and a number of candidate genes for renal stone disease. Quantitative biochemical traits that were predictive of renal stone disease were also analysed for linkage to the candidate regions. There was no evidence of linkage of the candidate gene loci with the renal stone phenotype or with the biochemical traits associated with renal stone disease. However the study did provide strong evidence for a quantitative trait locus affecting urinary citrate levels near the sodium-phosphate cotransporter 2 gene (NPT2) on chromosome 5q35 in one of the studied pedigrees.