title: Calcium kidney stones are associated with a haplotype of the calcium-sensing receptor gene regulatory region.
abstract: BACKGROUND
  Calcium-sensing receptor gene (CaSR) is a candidate to explain susceptibility to calcium kidney stones. Thus, we studied CaSR gene single-nucleotide polymorphisms (SNPs) and haplotypes associated with stones.
  
  
  METHODS
  Four hundred and sixty-three calcium stone formers and 213 healthy controls were genotyped for 21 SNPs mapping the whole CaSR gene. CaSR gene structure was studied. SNPs and haplotypes were analysed for association with stones.
  
  
  RESULTS
  Three haplotype blocks were identified in the CaSR gene. The first block was characterized by six SNPs and included gene promoters. The rs7652589 and rs1501899 SNPs and the CATTCA haplotype of the first block were significantly more frequent in normocitraturic calcium kidney stone formers than controls. The risk of stones was increased in normocitraturic homozygous patients and heterozygotes for the CATTCA haplotype. The rate of stones was higher in stone formers with the CATTCA haplotype. In a three-generation family, calcium stones were associated with the CATTCA haplotype. The bioinformatic analysis identified a new site for the octamer-binding transcription factor 1 in the presence of the variant alleles at the rs7652589 and rs1501899 SNPs. This transcription factor may downregulate the transcription of vitamin D-dependent genes and the CaSR expression. Conclusion. SNPs and CATTCA haplotype of the CaSR gene first block is associated with kidney stones in normocitraturic patients.
authors.affiliation: Nephrology and Dialysis Unit, Scientific Institute San Raffaele Hospital, Università Vita Salute University, Milan, Italy. vezzoli.giuseppe@hsr.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vezzoli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Terranegra
authors.forename: Teresa
authors.initials: T
authors.lastname: Arcidiacono
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gambaro
authors.forename: Luciano
authors.initials: L
authors.lastname: Milanesi
authors.forename: Ettore
authors.initials: E
authors.lastname: Mosca
authors.forename: Laura
authors.initials: L
authors.lastname: Soldati
mesh_terms: D000328:Adult; D002118:Calcium / Q000032:analysis*; D016022:Case-Control Studies; D002951:Citrates / Q000652:urine; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007669:Kidney Calculi / Q000737:chemistry* / Q000235:genetics* / Q000652:urine; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D012008:Recurrence
chemical_list: D002951:Citrates; D044169:Receptors, Calcium-Sensing; D002118:Calcium