Association of vitamin D receptor polymorphisms and nephrolithiasis: A meta-analysis.

Nephrolithiasis is a complex disease in which its pathophysiology is strongly influenced by genetics. Polymorphisms of the vitamin D receptor (VDR) gene have been reported to be associated with the development of kidney stones which in most cases are composed predominantly of calcium salts. For the purpose of this study, we performed a systematic review and meta-analysis to analyze the association of BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms with nephrolithiasis. A systematic search was performed up to June 2018 using PubMed, Embase and ISI Web of Knowledge databases. The keywords used for the search were “vitamin D receptor or VDR” and “polymorphisms or SNPs” combined with “urolithiasis or nephrolithiasis”. A meta-analysis was performed with the results of the selected and included studies. After analyzing 23 publications, we observed that BsmI polymorphism (rs1544410) has a protective association against nephrolithiasis (Allelic model: OR = 0.84, CI 95% 0.73–0.96, Z p-value 0.015; homozygous model: OR = 0.72, CI 95% 0.54–0.97, Z p-value 0.033). Furthermore, we observed that FokI polymorphism (rs2228570) has a decreased risk of nephrolithiasis in the heterozygous model in the presence of heterogeneity (OR = 0.69, CI 95% 0.48–0.99, Z p-value 0.044), as well as in the absence of heterogeneity (OR = 0.81, CI 95% 0.66–0.99, Z p-value 0.045). Additionally, TaqI polymorphism (rs731236) was associated with a decreased risk of nephrolithiasis in the heterozygous model (OR = 0.77, CI 95% 0.63–0.94, Z p-value 0.010), and no overall association was observed with ApaI polymorphism (rs7975232). This meta-analysis provided comprehensive evidence that VDR polymorphisms are associated with upper urinary tract stones incidence and the genetic variants we studied provide protection against nephrolithiasis.