Claudin-14 Gene Polymorphisms and Urine Calcium Excretion

Abstract

genotype at the 3' region is associated with calcium excretion in 24-hour urine and after the calciuretic stimulus of saline infusion.

Claudins in Renal Physiology and Pathology

“…Some single-nucleotide polymorphisms (SNPs) of CLDN14 are associated with 24 h urinary Ca 2+ excretion and/or kidney stones [148][149][150][151][152][153]. In silico analysis and in vitro studies of the SNP rs78250838:C> T suggest that it may introduce a novel insulinoma-associated 1 (INSM1) transcription factor binding site, enhancing CLDN14 mRNA and protein expression [151].…”

Inching toward a Greater Understanding of Genetic Hypercalciuria

“…The report by Arcidiacono et al (10) in this issue of the Clinical Journal of the American Society of Nephrology adds to our overall understanding of the regulation of calcium reabsorption in the thick limb, including the interaction between claudin genotypes and sodium loading. In this study, a total of 31 single-nucleotide polymorphisms (SNPs) in the 39 region of CLDN14 were associated with baseline calcium excretion in a cohort of subjects who were hypertensive.…”

“…Although it was long assumed that paracellular movements were the passive result of transcellular electrochemical gradients, it is now apparent that they are often highly selective on the basis of the relative expression of the tight junction claudin proteins initially described by Furuse and Tsukita (8). Currently, 27 claudins are known to impart selective permeabilities along the nephron (5,9,10). In the proximal tubule, claudin-2 is essential for maintaining paracellular water, sodium, and calcium permeability (5).…”

“…On the basis of in silico analyses, the SNP in the 39 region of CLDN14 that most associated with calcium excretion was predicted to influence splicing of its transcript, which in turn, could potentially alter protein-protein interactions of claudin-14 and claudin-16. A previous study found that the 62% of the general Icelandic population homozygous for the major allele of a CLDN14 SNP (rs219780) (4), implicated by Arcidiacono et al (10) in calcium excretion, had a 1.64-fold increased risk of nephrolithiasis (4). A Figure 1.…”

“…Although this study (10) was not designed or powered to detect an association of the measured claudin genotypes with nephrolithiasis, it still provides important insights regarding the potential contribution of claudin-14 to the human phenotype of hypercalciuria. Indeed, the body of evidence in the literature together with this study suggest that claudin-14 plays an important role regulating urinary calcium regulation in the general population and that genetic variation of this claudin modifies nephrolithiasis and osteoporosis risk.…”