Key genes and polymorphisms in urolithiasis associated with the formation of calcium oxalate, cystine and urate stones.
Authors:   the Department of general biology, pharmacognosy and botany, Head of the laboratory of cell technologies of the Center for experimental oncology of Saratov State Medical University n.a. V.I. Razumovsky, Ministry of Healthcare of the Russian Federation, Polukonova N.V. ,   Saratov, Russia, Khotko D.N. ,   the urological department of University Hospital №1 n.a. S.R. Mirotvortsev, Saratov State Medical University. V.I. Razumovsky, Ministry of Healthcare of the Russian Federation; Saratov, Russia, Bucharskaya A.B. ,   the laboratory of cell technologies of the Center for experimental oncology, Deputy Director of the Research Institute for Scientific Work of Saratov State Medical University n. a. V.I. Razumovsky, Ministry of Healthcare of the Russian Federation; Saratov, Russia, Khotko A.I. ,   the Department of Urology, Saratov State Medical University n.a. Razumovsky, Ministry of Health Care of the Russian Federation; Saratov, Russia, Tarasenko A.I. ,   the Institute of Urology and Reproductive Health of Sechenov First Moscow State Medical University. Sechenov First Moscow State Medical University (Sechenov University) Ministry of Health of Russia; Moscow, Russia, Popkov V.M. ,   the Department of Urology, Saratov State Medical University named after V.I. Razumovsky of the Ministry of Health of Russia; Saratov, Russia, Altynbayev R.R. ,   the State Medical Institution «SGKB No.8»; Saratov, Russia
Published: February 2025

Introduction. Urolithiasis is a multifactorial disease affecting all population groups. The incidence of urolithiasis in different countries varies from 1,7 to 14,8%. The risk of developing urolithiasis depends on age, gender, race, geographic location and hereditary predisposition, while 40-50% of patients have a burdened family history, so the search for genetic markers associated with urolithiasis is relevant.

Materials and methods. The search results were analyzed regardless of the date and language of publication in the scientific databases eLibrary, PubMed for the following keywords: urolithiasis, single nucleotide polymorphisms (SNP), calcium oxalate, cystine, urate stones. After analyzing the literature, 49 works were selected for review that most fully reflect the topic of key genes and polymorphism in urolithiasis associated with the formation of calcium oxalate, cystine and urate stones.

Results. The analysis has shown that the role of genetic factors in the formation of concrements of different composition is not equal. Oxalate calcium urolithiasis is a multifactorial disease associated with hypercalciuria, its determinant genes and SNPs: CALCR (rs1801197: «1377C>T»; «1340T>C» and «A>G»; rs1042138 (C>T), CaSR (rs6776158A>G of promoter 1), Klotho (rs1207568A>G; rs3752472T> C and rs650439), OPN (SPP1 rs2853744G>T) and VDR (ApaI (rs7975232) and TaqI (rs731236). SNPs in calcium oxalate urolithiasis are more often inherited by autosomal recessive type and localized in the coding or promoter regions of the gene, and the manifestation of the disease depends on ethnicity. Cystinuria is an inherited disease for which SNPs of two genes are re- sponsible: SLC3A1 with autosomal recessive inheritance (cystinuria type A, or type I) and SLC7A9 with incomplete recessive inheritance (cystinuria type B, or «not type I», types II and III). The genetic heterogeneity of cystinuria by SNP varies in different populations depending on the degree of its panmixis. The presence of type AB (SNPs in both genes) in patients suggests that cystinuria may be a digenetic disease. And the absence of mutations in patients with cystonuria indicates the involvement of not yet identified genes. Formation of hyperuricemia is a multifactorial disease, both with the participation of many rare and low-frequency SNPs of the gene SLC22A12, and with recessive inheritance of widespread SNP genes: SLC2A9, ABCG2.

Conclusions. The obtained data allow a personalized approach to treatment and prevention of oxalate, cystine and urate concretions in urolithiasis.