IngentaConnect Associations between renal sodium-citrate cotransporter (hNaDC-1)...

Authors: Okamoto, Naohiko¹; Aruga, Seiji; Matsuzaki, Shoji²; Takahashi, Satoru¹; Matsushita, Kazuo³; Kitamura, Tadaichi¹

Source: International Journal of Urology, Volume 14, Number 4, April 2007 , pp. 344-349(6)

Publisher: Blackwell Publishing

Abstract:

Purpose:

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. Materials and 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. Conclusion:

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.

Keywords: citrate; hypocitraturia; NaDC-1; recurrent renal stone former

Document Type: Research article

DOI: 10.1111/j.1442-2042.2007.01554.x

Affiliations: 1: Department of Urology, University of Tokyo, 2: Department of Urology, Inagi Municipal Hospital, and 3: Department of Urology, Tokyo Branch of the Tokai University Hospital, Tokyo, Japan

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Associations between renal sodium-citrate cotransporter (hNaDC-1) gene polymorphism and urinary citrate excretion in recurrent renal calcium stone formers and normal controls