title: Influence of calcium-sensing receptor gene on urinary calcium excretion in stone-forming patients.
abstract: Calcium-sensing receptor (CaSR) is a plasma membrane protein that regulates tubular reabsorption of Ca. To establish its role in idiopathic hypercalciuria, the association of urinary Ca excretion with the polymorphisms of CASR gene has been studied in healthy subjects and in hypercalciuric and normocalciuric Ca stone formers. CASR exon 7 single nucleotide polymorphisms (SNP), G/T at codon 986, G/A at codon 990, and C/G at codon 1011, were evaluated by PCR amplification and direct sequencing in 97 normocalciuric stone formers, 134 hypercalciuric stone formers, and 101 normocalciuric healthy controls. Four haplotypes were defined on the basis of CASR gene SNP: haplotype 1 was characterized by the most frequent sequence; haplotypes 2, 3, or 4 by the presence of a single polymorphic variant at codon 986, 990, or 1011, respectively. The relative risk of hypercalciuria was calculated with multinomial logistic regression and was significantly increased only in individuals carrying haplotype 3 (Odds ratio, 13.0 [95% confidence interval, 1.7 to 99.4]). Accordingly, Ca excretion was higher in subjects bearing haplotype 3, whereas those bearing haplotype 2 showed a slight increase of plasma Ca concentration. Multiple regression analysis showed that haplotype 3 explained 4.1% of the total variance of Ca excretion and 12.6% of the variance explained by the variables considered in the study. In conclusion, CASR gene could be a component of the complex genetic background regulating Ca excretion. Arg990Gly polymorphism could facilitate activation of CaSR and increase Ca excretion and susceptibility to idiopathic hypercalciuria.
authors.affiliation: Division of Nephrology Dialysis and Hypertension, Postgraduate School of Nephrology, Ateneo Vita e Salute, IRCCS San Raffaele Hospital, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vezzoli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Tanini
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Laura
authors.initials: L
authors.lastname: Soldati
authors.forename: Cristiana
authors.initials: C
authors.lastname: Bianchin
authors.forename: Francesco
authors.initials: F
authors.lastname: Franceschelli
authors.forename: Cecilia
authors.initials: C
authors.lastname: Malentacchi
authors.forename: Berardino
authors.initials: B
authors.lastname: Porfirio
authors.forename: Donatella
authors.initials: D
authors.lastname: Adamo
authors.forename: Annalisa
authors.initials: A
authors.lastname: Terranegra
authors.forename: Alberto
authors.initials: A
authors.lastname: Falchetti
authors.forename: Daniele
authors.initials: D
authors.lastname: Cusi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bianchi
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Brandi
mesh_terms: D002118:Calcium / Q000652:urine*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007669:Kidney Calculi / Q000235:genetics* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics*; D012016:Reference Values
chemical_list: D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D002118:Calcium