Calcium-sensing receptor gene polymorphisms in patients with calcium nephrolithiasis.
OBJECTIVE
The calcium-sensing receptor gene (CaSR, chr. 3q13.3-21) is a candidate to explain nephrolithiasis. This review analyzes the potential role of CaSR in lithogenesis according to findings of functional and genetic studies.


RESULTS
CaSR is a cation receptor located in the tubular cell plasma membrane. Its activation decreases calcium reabsorption in the ascending limb and distal convoluted tubule, but increases phosphate reabsorption in proximal tubules and decreases water and proton reabsorption in collecting ducts. Its effects in proximal tubules and collecting ducts can limit the calcium phosphate precipitation risk induced by the increase in calcium excretion. The nonconservative CaSR gene Arg990Gly polymorphism was associated with nephrolithiasis and hypercalciuria in different populations. Arg990Gly is located on exon 7 and produces a gain of the CaSR function. rs7652589 and rs1501899 were also associated with nephrolithiasis in patients with normal citrate excretion. These polymorphisms are located in the CaSR gene regulatory region and may modify CaSR gene promoter activity.


CONCLUSIONS
The activating Arg990Gly polymorphism may predispose to nephrolithiasis by increasing calcium excretion. Polymorphisms at the regulatory region may predispose to nephrolithiasis by changing tubular expression of the CaSR. CaSR genotype may be a marker to identify patients prone to develop calcium nephrolithiasis.
Nephrology and Dialysis Unit, San Raffaele Scientific Institute, Department of Medicine Surgery and Dentistry, Postgraduate School of Nephrology, Università degli Studi di Milano, Milan, Italy. vezzoli.giuseppe@hsr.it
Giuseppe
G
Vezzoli
Annalisa
A
Terranegra
Laura
L
Soldati
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005091:Exons; D020022:Genetic Predisposition to Disease; D006801:Humans; D053565:Hypercalciuria / Q000235:genetics / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D053040:Nephrolithiasis / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044169:Receptors, Calcium-Sensing / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic
C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing; D002118:Calcium