Abstract
Kidney stone disease is an urgent medical and social problem. Genetic factors play an important role in the disease development. This study aims to establish an association between polymorphisms in genes coding for proteins involved in calcium metabolism and the development of calcium urolithiasis in Russian population. In this case-control study, we investigated 50 patients with calcium urolithiasis (experimental group) and 50 persons lacking signs of kidney stone disease (control group). For molecular genetic analysis we used a previously developed gene panel consisting of 33 polymorphisms in 15 genes involved in calcium metabolism: VDR, CASR, CALCR, OPN, MGP, PLAU, AQP1, DGKH, SLC34A1, CLDN14, TRPV6, KLOTHO, ORAI1, ALPL, and RGS14. High-throughput target sequencing was utilized to study the loci of interest. Odds ratios and 95% confidence intervals were used to estimate the association between each SNP and risk of urolithiasis development. Multifactor dimensionality reduction analysis was also carried out to analyze the gene-gene interaction. We found statistically significant (unadjusted p-value < 0.05) associations between calcium urolithiasis and the polymorphisms in the following genes: CASR rs1042636 (OR = 3.18 for allele A), CALCR rs1801197 (OR = 6.84 for allele A), and ORAI1 rs6486795 (OR = 2.25 for allele C). The maximum OR was shown for AA genotypes in loci rs1042636 (CASR) and rs1801197 (CALCR) (OR = 4.71, OR = 11.8, respectively). After adjustment by Benjamini-Hochberg FDR we found only CALCR (rs1801197) was significantly associated with the risk of calcium urolithiasis development. There was no relationship between recurrent course of the disease and family history of urolithiasis in investigated patients. Thus we found a statistically significant association of polymorphism rs1801197 (gene CALCR) with calcium urolithiasis in Russian population.
Highlights
Kidney stone disease (KSD) has been known to be one of the most excruciating chronic diseases
The development of calcium urolithiasis has been attributed to polymorphisms in several genes: VDR, Case rs1042636 (CASR), CALCR, OPN, MGP, PLAU, AQP1, SLC34A1, CLDN14, KLOTHO, and ORAI1 (Filippova et al, 2020)
After the adjustment by Benjamini-Hochberg procedure no statistically significant differences between KSD patients and controls were found for the rs219780 (CLDN14) and rs1042636 (CASR)
Summary
Kidney stone disease (KSD) has been known to be one of the most excruciating chronic diseases. It is believed that the vast majority of cases are, multifactorial. Deciphering the molecular substrate for the etiopathogenesis of urolithiasis is of outmost importance for developing diagnostic tools and therapy strategies. KSD is caused by the formation of calcium concrements, supplying grounds for research into the calcium metabolism impairments in those affected by the disease. Numerous works have been published that elucidate hidden associations between polymorphisms in genes of calcium metabolism and the development of KSD (Filippova et al, 2020). The development of calcium urolithiasis has been attributed to polymorphisms in several genes: VDR, CASR, CALCR, OPN, MGP, PLAU, AQP1, SLC34A1, CLDN14, KLOTHO, and ORAI1 (Filippova et al, 2020)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
