Claudin-14 Gene Polymorphisms and Urine Calcium Excretion.

BACKGROUND AND OBJECTIVES

Claudin-16 and -19 are proteins forming pores for the paracellular reabsorption of divalent cations in the ascending limb of Henle loop; conversely, claudin-14 decreases ion permeability of these pores. Single-nucleotide polymorphisms in gene coding for were associated with kidney stones and calcium excretion. This study aimed to explore the association of , , and single-nucleotide polymorphisms with calcium excretion.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective observational study of 393 patients with hypertension who were naïve to antihypertensive drugs, in whom we measured 24-hour urine calcium excretion; history of kidney stones was ascertained by interview; 370 of these patients underwent an intravenous 0.9% sodium chloride infusion (2 L in 2 hours) to evaluate the response of calcium excretion in three different 2-hour urine samples collected before, during, and after saline infusion. Genotypes of , , and were obtained from data of a previous genome-wide association study in the same patients.

RESULTS

Thirty-one single-nucleotide polymorphisms of the 3' region of the gene were significantly associated with 24-hour calcium excretion and calcium excretion after saline infusion. The most significant associated single-nucleotide polymorphism was rs219755 (24-hour calcium excretion in GG, 225±124 mg/24 hours; 24-hour calcium excretion in GA, 194±100 mg/24 hours; 24-hour calcium excretion in AA, 124±73 mg/24 hours; <0.001; calcium excretion during saline infusion in GG, 30±21 mg/2 hours; calcium excretion during saline infusion in GA, 29±18 mg/2 hours; calcium excretion during saline infusion in AA, 17±11 mg/2 hours; =0.03). No significant associations were found among and single-nucleotide polymorphisms and calcium excretion and between , , and single-nucleotide polymorphisms and stones. Bioinformatic analysis showed that one single-nucleotide polymorphism at among those associated with calcium excretion may potentially influence splicing of transcript.

CONCLUSIONS

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