Predisposition of genetic polymorphism with the risk of urolithiasis

Abstract

Urolithiasis is a relevant clinical problem with a subsequent burden for health system. The aim of this review is to provide recent progress made using genetic polymorphisms to define pathophysiology, to identify persons at risk for kidney stone disease and to predict treatment response. Population case-control studies are useful both as an alternative and an adjunct as compared to family studies. These involve either whole genome scanning or candidate gene approaches. While whole genome scanning is likely to be widely used in future, at present, candidate gene studies are more feasible. When performing candidate gene case-control studies factors such as study design, methods for recruitment of case and controls, selection of candidate genes, functional significance of polymorphisms chosen for study and statistical analysis require close attention to ensure that only genuine associations are detected. Some of the significant genes that play role in stone formation include calcitonin receptor gene (CTR), vitamin D receptor (VDR), Urokinase, Interleukin, (IL-1β, IL-Ra), E-Cadherin, Androgen & oestrogen receptor gene, vascular endothelial growth factor (VEGF) and Arginine p21. In our case-control study we studied CTR, VDR, Urokinase, IL-1β(-511 and +3954), IL-Ra from north India and predict that VDR, IL-β (-511) and IL-1Ra gene may be used as a possible genetic marker for earlier detection in patients who are at risk for calcium oxalate stone disease. Further, linkage disequilibrium and haplotype structure of a certain candidate gene is important for association analysis. When a certain polymorphic allele has been found to be associated with disease, it is further explained on basis of LD and haplotype structure by one or more other alleles. Once it is determined which haplotype carries the risk allele, by means of molecular biological functional analyses, the variants on that haplotype allele truly causing the effect can be determined.

ApaL1 urokinase and Taq1 vitamin D receptor gene polymorphisms in first-stone formers, recurrent stone formers, and controls in a Caucasian population

“…One SNP of interest is the ApaL1 C/T SNP located at the 3′-untranslated region (UTR) of the urokinase gene on chromosome 10 [2]. It has been proposed that the fibrinolytic function of urinary urokinase may prevent the formation of organic matrix in the urinary tract [3], a major step in urinary stone formation [4]. Another candidate gene is the vitamin D receptor (VDR) Abstract The purpose of this study was to determine differences in genotype distribution and allele frequency of urokinase and vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) between first-stone formers, recurrent stone formers, and controls in a Caucasian population.…”

The role of vitamin D receptor gene polymorphisms in Turkish infants with urolithiasis

“…Susceptibility genes for stone disease are the VDR gene, calcitonin receptor gene, interleukin 1 gene cluster, urokinase gene, arginine p21, VEGF, AR&ER receptor, and e-cadherin gene. 17 The most popular is the VDR gene, which is 5.6 kb in size and is located on chromosome 12q12-14. VDR is related to genomic and non-genomic effects of 1.25(OH)D on renal tubular cells and modulates citrate metabolism and transport of calcium and phosphate.…”

“…Linkage disequilibrium is the nonrandom association of alleles at linked loci and is required to assess genes predisposition to complex diseases, such as urolithiasis. 17,20,21 Many studies have shown that VDR gene polymorphism has an undeniable relationship with urolithiasis and hypercalciuria. Hypercalciuria may result from increased calcium absorption and decreased renal calcium or phosphorus reabsorption and/or enhanced bone demineralization.…”

Gene variants of osteoprotegerin, estrogen-, calcitonin- and vitamin D-receptor genes and serum markers of bone metabolism in patients with Gaucher disease type 1

“…28 For the CALCR gene c.1340T.C; rs1801197 variant, the genotypes were determined as previously described. 29 For the VDR c.1024+283G.A; rs1544410 gene variant, we used a protocol described by Kaya et al 30 The PCR reactions were prepared in a 25 Thermo Fisher Scientific). The digestion products were resolved in 3% high-resolution agarose gel electrophoresis (MetaPhor, Lonza, Basel, Switzerland) and stained with RedSafe (Chembio Ltd, Rickmansworth, UK) for visualization on a UV transilluminator.…”