The G Allele of CaSR R990G Polymorphism Increases Susceptibility to Urolithiasis and Hypercalciuria: Evidences from a Comprehensive Meta-Analysis

Abstract

Background. The calcium-sensing receptor gene (CaSR) is a candidate to explain urolithiasis. A number of case-control studies were conducted to investigate associations between CaSR polymorphisms with risks of hypercalciuria and urolithiasis in humans. But the results were still inconsistent. Methods. A meta-analysis was performed to address this issue. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of associations between CaSR polymorphisms and the risk of urolithiasis. The pooled standardized mean difference (SMD) with 95% CI was used for the meta-analysis of CaSR polymorphisms and urine calcium concentration. Results. For urolithiasis association, the SS genotype of A986S polymorphism was a risk factor for urolithiasis in Asians and PHPT patients, but a protective factor in Caucasians. The GG genotype of R990 polymorphism was associated with an increased risk of urolithiasis, especially in Caucasians and healthy population. Regarding urine calcium concentration association, individuals with the G allele had a higher level of urine calcium than the noncarriers. Conclusions. This meta-analysis revealed that the G allele of CaSR R990G polymorphism increases susceptibility to urolithiasis and hypercalciuria. The A986S and Q1011E polymorphisms were associated with urolithiasis and hypercalciuria in specific populations.

Calcium-Sensing Receptor Genetic Polymorphisms and Risk of Developing Nephrolithiasis in a Chinese Population

“…Kim et al [27] , in a study on 433 patients and 197 controls, observed no statistically significant differences between the patient groups and the control for Ala986Ser SNP. Moreover, Liu et al [28] conducted a meta-analysis including 1,049 subjects and found that the G allele of R990G polymorphism might contribute a significant increased overall risk of urolithiasis. These data strongly support our findings that the Arg990Gly rather than Ala986Ser SNP is likely to be associated with the risk of developing nephrolithiasis.…”

Association between calcium-sensing receptor (CaSR) R990G, CaSR A986S, and CaSR Q1011E gene polymorphisms and the risk of urolithiasis: a meta-analysis

“…For this reason, we also evaluated the role of CaSR Q1011E gene polymorphism in patients with urolithiasis. Although Q allele was reported to be associated with elevated calcium concentration and hypercalciuric state [27], and previous meta-analysis also confirmed that CaSR Q1011E gene polymorphism was associated with urolithiasis in specific population [18]; however, of five papers we collected [27,32,33,38,39], all of them failed to show the association. Our pooled calculation also revealed that no association was found in all genetic models between CaSR Q1011E gene polymorphism and the risk of urolithiasis.…”

“…To date, the perspective theory underlying our results was lacking. However, several studies had reported that increased CaSR activity was observed in S allele of CaSR A986S gene polymorphism [18]. Moreover, S allele of CaSR A986S was also reported to be associated with the decrease of inhibitory activity of CaSR on tubular calcium reabsorption [28].…”

“…A previous study [18] had reported the meta-analysis concerning this topic. Overall, our results were consistent with this previous study.…”

“…To date, the reports concerning those SNPs in patients with urolithiasis were inconclusive. Furthermore, previous metaanalysis [18] in this circumstance did not suffice to establish a potent conclusion because of some limitations.…”