title: Associations between renal sodium-citrate cotransporter (hNaDC-1) gene polymorphism and urinary citrate excretion in recurrent renal calcium stone formers and normal controls.
abstract: OBJECTIVE
  Urinary citrate is a potent inhibitor of renal stone formation. Its excretion is regulated by Na(+)/dicarboxylate cotransporter-1 (NaDC-1), which is expressed on the apical membrane of renal proximal tubules. Many patients with calcium urolithiasis exhibit hypocitraturia, however, the mechanisms are not perfectly understood. We examined whether or not the I550V polymorphism in human NaDC-1 gene (hNaDC-1) influenced urinary citrate excretion.
  
  
  METHODS
  I550V polymorphism was investigated in 105 patients with recurrent renal calcium stone formation (RSF) and 107 age-matched healthy volunteers with non-renal stone formation (NSF), using polymerase chain reaction (PCR) restriction fragment length polymorphism analysis and two 24-h urine samples.
  
  
  RESULTS
  Overall and in the RSF groups, subjects with a BB (homozygous for the digested Bcl-I allele) genotype exhibited a significantly lower urinary citrate excretion level than subjects with a bb (homozygous for the undigested allele) genotype. Genotype distributions between subjects with hypocitraturia and normocitraturia were significantly different, with the BB genotype being more frequently observed in subjects with hypocitraturia - both overall and in each of the RSF and NSF groups. Although the BB genotype was observed more frequently in the RSF group than in the NSF group, no statistical differences among the distributions of the three genotypes (BB, Bb [heterozygous] and bb) were observed between the RSF and NSF groups.
  
  
  CONCLUSIONS
  These results suggest that the B allele of I550V polymorphism of hNaDC-1 may be associated with a reduction in urinary citrate excretion and contribute to hypocitraturia in recurrent renal stone formers.
authors.affiliation: Department of Urology, University of Tokyo, Tokyo, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Okamoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Aruga
authors.forename: Shoji
authors.initials: S
authors.lastname: Matsuzaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Matsushita
authors.forename: Tadaichi
authors.initials: T
authors.lastname: Kitamura
mesh_terms: D016022:Case-Control Studies; D019343:Citric Acid / Q000652:urine*; D029382:Dicarboxylic Acid Transporters / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007669:Kidney Calculi / Q000235:genetics* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012008:Recurrence; D027981:Symporters / Q000235:genetics*
chemical_list: D029382:Dicarboxylic Acid Transporters; D029363:Organic Anion Transporters, Sodium-Dependent; C092524:SLC13A2 protein, human; D027981:Symporters; D019343:Citric Acid