E-cadherin gene 3'-UTR C/T polymorphism is associated with prostate cancer

INTRODUCTION: E-cadherin (CDH-1) is a cell-cell adhesive molecule which maintains cell integrity and communication between the intracellular and extracellular world. CDH-1 may therefore be related to carcinogenesis. A polymorphism located at the 3'-UTR of the CDH-1 gene is associated with stone disease; however, its relationship to prostate cancer has not been reported. We aimed to study whether there is an association between the 3'-UTR polymorphism and prostate cancer. MATERIALS AND METHODS: We collected 96 patients with prostate cancer and 114 normal controls for this study. The polymorphism of the CDH-1 gene was studied by polymerase chain reaction-based restriction analysis. RESULTS: There was a significant difference in genotype distribution of the CDH-1 gene polymorphism between cancer patients and normal controls (p < 0.001). The distribution of the CDH-1 gene CC genotype in prostate cancer patients (51.0%) was higher than in the controls (10.5%). The odds ratio for the CDH-1 'C' allele was 2.896 (95% CI = 1.908-4.396). There was no significant difference according to age, pathological grading, clinical staging, and responsiveness to hormonal therapy among patients. Only 3 patients (3.1%) had a history of urolithiasis. CONCLUSIONS: The CDH-1 gene 3'-UTR C/T polymorphism is associated with prostate cancer. The 'CC' homozygote indicates a relatively higher risk for developing prostate cancer than other genotypes.     

Association of urokinase gene 3′-UTR T/C polymorphism with calcium oxalate urolithiasis in children

INTRODUCTION AND OBJECTIVES: Urokinase is synthesized by various cells such as kidney, pneumocytes, and phagocytes. It cleaves plasminogen to plasmin and hence stimulates fibrinolysis. Urokinase breaks down the matrix protein within the stone and thus prevents stone formation and growth. Urokinase concentrations are lower and urokinase gene 3'-UTR T/C polymorphism is higher in patients with recurrent stones. Our aim was to investigate the role of urokinase gene 3'-UTR T/C polymorphism in childhood recurrent stone disease. MATERIAL AND METHODS: A control group of 40 healthy children having no history of stone formation (group 1) (mean age 10.5 +/- 4.2 years), 40 children (mean age 10.5 +/- 4.33 years) who had calcium oxalate stones for the first time (group 2), and 40 patients (mean age 11.2 +/- 3.8 years) with recurrent calcium oxalate stone disease (group 3) were included in the study. The groups were compared with respect to age, gender and urokinase gene 3'-UTR T/C polymorphism. Polymerase chain reaction-based restriction analysis was used to identify C/T polymorphism of the urokinase gene. RESULTS: No significant difference was observed between the three groups with respect to age and gender, while urokinase gene 3'-UTR T/C gene polymorphism was observed in four patients (10%) from group 3. In groups 1 and 2 there was no patient with T/C polymorphism. CONCLUSIONS: Urokinase 3'-UTR T/C gene polymorphism seems to appear more commonly in children with recurrent calcium oxalate stone disease than in healthy children and in those with stones for the first time. These results suggest that the urokinase gene might play a role in childhood recurrent calcium oxalate stone disease.     

Calcitonin receptor gene polymorphism: a possible genetic marker for patients with calcium oxalate stones.

OBJECTIVES: The formation of urinary stones is hypothesized to be associated with calcitonin receptors. The most commonly seen polymorphism is C/T at the 1377th nucleotide. Hence, these polymorphisms are being used as a genetic marker in the search for the cause of urolithiasis. METHODS: A normal control group of 105 healthy people and 102 patients with recurrent calcium oxalate stones were examined. The polymorphism was detected following a polymerase chain reaction-based and restriction analysis by AluI. An uncuttable length is 228 bp (CC) whereas two fragments of 120 and 108 bp are shown as cuttable lengths (TT). RESULTS: The results revealed significant differences between the normal individuals and the stone patients (p<0.01). The distribution of leucine (cuttable) homozygote in the stone group (2.0%) was higher than in the control group (0.0%). The odds ratio for the leucine allele of the calcitonin receptor gene in calcium oxalate stone disease is 5.634 (95% CI: 2.286--13.885). CONCLUSIONS: Results show that the polymorphism in the calcitonin receptor gene could be a genetic marker for urinary stone disease and therefore it is worthwhile pursuing further studies of the leucine allele of calcitonin receptor gene due to it is strongly correlated with stone disease.     

TAP 2 gene Msp-I polymorphism might be associated with calcium oxalate stone disease

INTRODUCTION: Inflammation might be one of the causes of stone disease. The function of the transporter associated with antigen-processing protein (TAP) is related to immune response and inflammation. Our aim was to investigate the relationship between stone disease and 5 polymorphic sites of the TAP gene (TAP1-1, 1-2, 2-1, 2-2, 2-3). MATERIALS AND METHODS: We compared the frequencies of 5 polymorphisms in the TAP gene between 208 patients with recurrent calcium oxalate stone and 210 healthy controls. The polymorphism was detected by polymerase chain reaction-based restriction analysis. RESULTS: Significant differences in the frequency of the polymorphism at the TAP2-2 site were detected between normal individuals and calcium stone disease patients (p<0.0001). The distribution of the genotype AA homozygote was higher in stone patients (33.3%) than in the control group (16.3%). The odds ratio for the A allele compared with the G allele was 2.097 (95% CI 1.571-2.802). CONCLUSIONS: We conclude that the TAP2-2 MspI polymorphism might be associated with calcium stone disease.     

Vascular endothelial growth factor gene polymorphism is associated with calcium oxalate stone disease

Growth factor-related genes regulate cell growth, differentiation and apoptosis in the kidney in response to cellular injury. One of the theories of stone formation is that cellular injury, and thus growth factors, play a role. We therefore investigated the association between growth factor genes and calcium oxalate stone disease. The most frequently seen polymorphism of the vascular endothelial growth factor (VEGF) gene is Bst U I C/T, which is located upstream at the -460th nucleotide. Other growth factor-related gene polymorphisms include the cytochrome P450c17alpha enzyme (CYP17) gene MspA I C/T polymorphism at the 5'-UTR promoter region, the epidermal growth factor receptor (EGFR) gene Bsr I polymorphism (A to T) at position 2,073, and the insulin-like growth factor-2 (IGF-2) gene Apa I A/G at exon 9. All four polymorphisms were used as genetic markers in this study in the search for an association between stone disease and growth factor related genes. A normal control group of 230 healthy people, and 230 patients with calcium oxalate stone, were examined. The polymorphism was seen following polymerase chain reaction based restriction analysis. The result revealed a significant difference between normal individuals and stone patients (P=0.0003, Fisher's exact test) in the distribution of the VEGF gene polymorphism as well as an odds ratio of 1.30 (95% confidence interval=0.993-1.715) per copy of the "T" allele. Whereas, the IGF-2, EGFR and CYP17 gene polymorphisms did not reveal a significant association with stone disease. We conclude that the VEGF gene Bst U I polymorphism is a suitable genetic marker of urolithiasis.     

Lack of evidence for the association of tumor necrosis factor-alpha gene promoter polymorphism with calcium oxalate stone and bladder cancer patients

Urinary stone disease and bladder cancer are two of the most commonly seen urologic diseases in Taiwan. Tumor necrosis factor-alpha (TNF-alpha) is one of the cytokines secreted by macrophages and is related to a sequence of events in response to inflammation and cancer formation. We investigated the polymorphism of the TNF-alpha gene promoter -308 as a genetic marker in searching for the association between these two commonly seen urologic diseases. One hundred and fourteen patients with transitional cell carcinoma of the urinary bladder and 103 patients with calcium oxalate stone were compared with 150 healthy controls. The polymorphism was detected by polymerase chain reaction-based restriction analysis (Nco I endonuclease). The results revealed no significant differences between normal individuals and the patients with the two commonly seen urologic diseases (P > 0.05). We concluded that the polymorphism of the TNF-alpha promoter -308 is not a valid genetic marker for these two urologic diseases.     

Arginine form of p21 gene codon 31 is less prominent in patients with calcium oxalate stone

The formation of urinary stones is associated with cell death in response to various injuries. P21 (WAF1/CIP1) is a downstream protein of P53 and can arrest the cell cycle at G1/S with resulting cell death. We aimed to investigate the polymorphism of p21 gene codon 31 as the genetic marker in searching for the association of urolithiasis. One hundred and nineteen healthy controls and 95 patients with calcium oxalate stone were examined in this study. The polymorphism was seen from the result of polymerase chain reaction-based restriction analysis. The result revealed significant differences between normal individuals and stone patients (P < 0.05) and the distribution of arginine homozygote in the control group (31.9%) was higher than in the patient group (16.8%). It is concluded that polymorphisms of p21 codon 31 can be a genetic marker for urinary stone disease. Individuals possessing arginine form of p21 codon 31 have less risk of developing calcium stone disease. Received: 15 June 2000 / Accepted: 6 December 2000     

Association of the vitamin D receptor gene start codon Fok I polymorphism with calcium oxalate stone disease

OBJECTIVE: To assess the use of Fok I polymorphism (the most frequent polymorphism, at the start codon of the vitamin D receptor gene, VDR) as a convenient genetic marker in identifying the cause of urolithiasis. PATIENTS, SUBJECTS AND METHODS: A normal control group of 90 healthy subjects and 146 patients with calcium oxalate stones were examined. Using polymerase chain reaction (PCR)-based restriction analysis, the relationship between Fok I polymorphism and urolithiasis was evaluated. An unexcisable length of 265 bp was identified (allele CC) and two fragments (169 bp and 96 bp) identified as excisable lengths (allele TT). RESULTS: There was a statistically significant difference between the groups (chi-square test, P < 0.05) for the genotype of the VDR Fok I start codon polymorphism. The odds ratio (95% confidence interval) for the C allele in those at risk of stone disease was 1.672 (1.149-2.432). CONCLUSIONS: These results suggest that the VDR Fok I start codon polymorphism may be a good candidate for a genetic marker in calcium oxalate stone disease.     

Association of vitamin D receptor-gene (FokI) polymorphism with calcium oxalate nephrolithiasis

BACKGROUND AND PURPOSE: Formation of kidney stones is still not understood but is hypothesized to be associated with the vitamin D receptor gene (VDR). In order to assess the eventual role of VDR start-codon FokI polymorphism in stone formation, we evaluated the association between calcium stone disease and this polymorphism in a North Indian population. PATIENTS AND METHODS: A control group comprised of 166 healthy individuals (age range 22-58 years) and a group of 138 patients with calcium oxalate stones (age range 21-72 years) were examined. The polymorphism was detected using polymerase chain reaction-based restriction analysis. An unexcisable length of 265 bp (CC) and two fragments of 169 bp and 96 bp (TT) were obtained by FokI restriction digestion. RESULTS: There was a statistically significant difference between the control and patient groups (X2 test, P<0.001) for the genotype of the VDR FokI start-codon polymorphism. The odds ratio (with 95% CI) for the C allele in those at risk of stone disease was 1.654 (1.041, 2.628). The VDR frequency distribution was also statistically significant (P<0.001) in case of male sex. The frequency distribution for this genetic polymorphism was not statistically different in normocalciuric and hypercalciuric stone patients (P=0.355). CONCLUSION: The VDR FokI polymorphism may be a good candidate for a marker for calcium oxalate-stone disease. These findings may contribute a small piece to the understanding of the pathogenesis of urinary calculi.     

Osteocalcin gene Hind III polymorphism is not correlated with calcium oxalate stone disease

The formation of urinary stones is presumed to be associated with polymorphism of the osteocalcin gene. The most frequently seen polymorphism is the Hind III type located at the promoter region. This polymorphism has been used as a genetic marker in the search for a correlation between urolithiasis and normal subjects. In our study, a normal control group of 105 healthy people and 102 patients with calcium oxalate stones were examined. The polymorphism was seen following polymerase chain reaction-based restriction analysis. The results revealed no significant differences between normal individuals and stone patients (P=0.978), and distribution of the TT homozygote in the control group (42.9%) was similar to that in the patient group (42.2%). Further categorization of the stone patients into normocalciuric and hypercalciuric groups also revealed no statistical differences from controls. We conclude that Hind III polymorphism of the osteocalcin gene is not a suitable genetic marker of urinary stone disease. Further searches for other polymorphisms on this gene correlated with stone disease are suggested. Received: 25 August 2000 / Accepted: 27 December 2000     

Interleukin-1β gene and receptor antagonist gene polymorphisms in patients with calcium oxalate stones

Interleukin-1 (IL-1) might play a role in the process of bone loss and hypercalciuria and is therefore considered to be involved in the formation of urinary stones. The aim of this study is to test whether the IL-1beta promoter region, exon 5 region and IL-1 receptor antagonist gene intron 2 polymorphisms could be genetic markers for the susceptibility to the formation of urinary stones. A control group of 152 healthy people and a group of 105 patients with recurrent calcium oxalate stone were examined in this study. Polymerase chain reaction (PCR) analyzed the variable number tandem repeats at intron 2 of the IL-1Ra gene for the polymorphisms. PCR-based restriction analysis was done for the IL-1beta gene polymorphisms of the promoter region and exon 5 by the endonucleases Ava I and Taq I, respectively. The polymorphisms studied in the IL-1beta genes did not reveal a strong association with calcium oxalate stone disease when compared with the control group (promoter region by chi-square test, P=0.627: exon 5 region by Fisher's exact test, P = 0.403). Only two frequent alleles of the IL-1Ra gene corresponding to one and two copies of an 86-bp sequence repeat were identified by PCR. The result revealed significant differences between control individuals and stone patients (P < 0.01. Fisher's exact test). In addition, the frequency of the type I allele in the stone group (99.0%) was higher than in the control group (94.0%). The odds ratio for the type I allele of the IL-1Ra gene in calcium oxalate stone disease is 6.041 (95% CI: 1.683 approximately 21.687). There is an association between urolithiasis and polymorphism in the IL-1Ra gene. No significant difference was found when dividing the stone patients into groups with normocalciuria and hypercalciuria in relation to these genetic polymorphisms. Further studies of the type I allele of the IL-IRa gene are worthwhile because of its correlation with stone disease. In our study, neither the IL-1beta promoter region nor the exon 5 polymorphisms were significantly different when comparing control subjects and calcium oxalate stone patients.     

Association of vitamin D receptor gene polymorphism with urolithiasis

PURPOSE: Recent studies suggest that allelic variations of the vitamin D receptor (VDR) gene can influence calcium absorption and excretion. Therefore, we studied the association of VDR gene polymorphism with urolithiasis. SUBJECTS AND METHODS: We studied 83 patients with urinary stones and 83 controls. Patients were scored for certain clinical characteristics, including long axis diameter of the largest stone (1 point-less than 10 mm. and 2-10 mm. or greater), number of stones (1 point-1 and 2-multiple) and history of calcium stone disease (1 point-absent and 2-present). They were classified into 3 groups according to the total score, including low-3, intermediate-4 or 5 and high-6 points. The 2 VDR gene polymorphisms TaqI and ApaI were detected by polymerase chain reaction-restriction fragment length polymorphism and their relationships with the urinary calcium level were examined. RESULTS: The incidence of TaqI Tt and tt genotypes was significantly higher in the high score group than in controls. The TaqI t allele was associated with a 5.2-fold increase in the risk of severe stone disease. The urinary calcium level in patients with the Tt and tt genotypes was also higher than in those with the TT genotype. The rate of the ApaI genotype was not different in the high score group and controls. CONCLUSIONS: The TaqI t allele of the VDR gene may be a risk factor for severe stone disease and recurrent stones.     

Prediction of stone disease by discriminant analysis and artificial neural networks in genetic polymorphisms: a new method

OBJECTIVE: To use information from genetic polymorphisms and from patients (drinking/exercise habits) to identify their association with stone disease, the main analytical and predictive tools being discriminant analysis (DA) and artificial neural networks (ANNs). PATIENTS, SUBJECTS AND METHODS: Urinary stone disease is common in Taiwan; the formation of calcium oxalate stone is reportedly associated with genetic polymorphisms but there are many of these. Genotyping requires many individuals and markers because of the complexity of gene-gene and gene-environmental factor interactions. With the development of artificial intelligence, data-mining tools like ANNs can be used to derive more from patient data in predicting disease. Thus we compared 151 patients with calcium oxalate stones and 105 healthy controls for the presence of four genetic polymorphisms; cytochrome p450c17, E-cadherin, urokinase and vascular endothelial growth factor (VEGF). Information about environmental factors, e.g. water, milk and coffee consumption, and outdoor activities, was also collected. Stepwise DA and ANNs were used as classification methods to obtain an effective discriminant model. RESULTS: With only the genetic variables, DA successfully classified 64% of the participants, but when all related factors (gene and environmental factors) were considered simultaneously, stepwise DA was successful in classifying 74%. The results for DA were best when six variables (sex, VEGF, stone number, coffee, milk, outdoor activities), found by iterative selection, were used. The ANN successfully classified 89% of participants and was better than DA when considering all factors in the model. A sensitivity analysis of the input parameters for ANN was conducted after the ANN program was trained; the most important inputs affecting stone disease were genetic (VEGF), while the second and third were water and milk consumption. CONCLUSIONS: While data-mining tools such as DA and ANN both provide accurate results for assessing genetic markers of calcium stone disease, the ANN provides a better prediction than the DA, especially when considering all (genetic and environmental) related factors simultaneously. This model provides a new way to study stone disease in combination with genetic polymorphisms and environmental factors.     

Coding region analysis of vitamin D receptor gene and its association with active calcium stone disease

The purpose of this study was to evaluate the impact of vitamin D receptor (VDR) gene polymorphisms on the status of active renal calcium stone formation. Male active renal calcium stone formers (ASF, final N = 106) with two episodes of stone relapse in the past 5 years were enrolled from December 2008 to April 2009. Controls (N = 109) were selected from age range- and gender-matched individuals who had no evidence or history of stone disease. Sequencing and single-strand conformational polymorphism were used to determine VDR polymorphisms in the patients and controls. Three polymorphisms were identified in the VDR gene: (1) start codon polymorphism (rs2228570T>C; p.M1T); (2) C/T polymorphism in the second intron (NT-029419.12: g.10416049C>T); (3) a silent polymorphism in exon 9 (rs731236T>C; p.I352I). Start codon polymorphism was the only one that was associated with the status of calcium stone formation (p < 0.05). We performed a complete coding genome analysis of VDR gene and observed that only start codon polymorphism was related to the status of active calcium stone formation.     

Association of Urokinase Gene 3'-UTR T/C polymorphism with bladder cancer

INTRODUCTION: Bladder cancer is a disease characterized by multiple recurrences. Some investigators assume urokinase to be involved in the causation of bladder cancer, although there is lack of genetic evidence. Our aim was to evaluate whether polymorphism of the urokinase gene is associated with transitional cell carcinoma (TCC) of the urinary bladder. MATERIALS AND METHODS: The study included 100 patients (mean age 62.5 +/- 10.2 years) with TCC of urinary bladder and 150 healthy controls (mean age 60 +/- 11.5 years) living in the same area. Polymerase chain reaction (PCR)-based restriction analysis was used to identify the C/T polymorphism of the urokinase gene. Genotyping distribution and allelic frequencies between patients and controls were compared. RESULTS AND CONCLUSION: There was a significant difference in the frequency distribution of the urokinase gene 3'-UTR C/T polymorphism in bladder cancer patients as compared to the normal control group (p < 0.05), but no significant difference in allelic frequencies or in carriage rates between bladder cancer patients and normal controls were observed. Our study suggests that urokinase gene polymorphism may be associated with bladder cancer and can thus serve as a potential genetic marker in screening for the possible causes of bladder cancer. Perhaps analysis of patients with superficial bladder TCC and mutated urokinase might help clarify this aspect in large cohort studies in different populations.     

A polymorphism of matrix Gla protein gene is associated with kidney stones

PURPOSE: Matrix Gla protein, a potent calcification inhibitor in arterial vessels, is also expressed in the kidney and is up-regulated following the administration of ethylene glycol, a precursor of oxalate. Considering the analogous characteristics between arterial calcification and kidney stones, we identified variants of the human matrix Gla protein gene and investigated whether there is an association between MGP genetic polymorphisms and kidney stones. MATERIALS AND METHODS: We studied single nucleotide polymorphisms in matrix Gla protein in 122 kidney stone cases and 125 controls. We resequenced the human genomic MGP gene, including the 1,000 bp promoter 5'-untranslated region, 4 exons and 3'-untranslated regions, and we performed systematic genetic analysis. A single nucleotide polymorphism was genotyped using a fluorescent 5'endonuclease assay and its association with kidney stones was analyzed. RESULTS: We observed 19 polymorphisms. A single nucleotide polymorphism was associated with kidney stones (OR 0.51, 95% CI 0.30-0.87; p = 0.012). The G allele carrier had a 2-fold decreased kidney stone risk compared with A allele carriers in single nucleotide polymorphism 11 (OR 0.55, 95% CI 0.31-1.00, p = 0.047). We found no association between the polymorphism and kidney stone clinical characteristics. CONCLUSIONS: Our findings show that an MGP gene polymorphism is associated with kidney stones and influences genetic susceptibility to kidney stones. In the future functional assays of the polymorphism should permit better understanding of the role of matrix Gla protein genetic variants and kidney stones.     

Polymorphism of vitamin D receptor gene start codon in patients with calcium kidney stones

BACKGROUND: A linkage has been detected between vitamin D receptor (VDR) locus and calcium kidney stone disease. In order to assess the eventual role of VDR gene start codon polymorphisms in stone production, we analyzed the genotype-phenotype association in a group of patients with calcium kidney stones. METHODS: One hundred and fifty-five patients were studied. VDR genotypes were characterized at the translation start site by restriction fragment length polymorphism analysis, using endonuclease FokI. Phenotypes of calcium-phosphate metabolism were compared in patients with different genotypes: strontium enteral absorption (used as a surrogate marker for calcium absorption), bone mineral density (BMD), calcium and phosphate excretion were measured. RESULTS: Genotype distribution was not different in hypercalciuric and normocalciuric stone formers. Enteral strontium absorption, calcium excretion and BMD did not vary with the patient's genotype. Serum concentrations of phosphate (p=0.022) and renal threshold for phosphate excretion (p=0.026) were lower in patients with genotype FF (homozygous for the absence of the FokI site) than in those with genotype ff (homozygous for the presence of the FokI site). The lower phosphatemia was confirmed in FF hypercalciuric patients, but not in normocalciuric ones. Serum concentrations of phosphate and calcitriol in the group of hypercalciuric patients were inversely correlated with the genotype FF. CONCLUSIONS: The FokI genotype does not appear to be involved in the causes of idiopathic hypercalciuria and kidney stones. Hypercalciuric patients with FF genotype may be a subgroup with low plasma concentrations of phosphate, predisposed to tubular leakage of phosphate.     

Vitamin D receptor Fok1 polymorphisms affect calcium absorption, kinetics, and bone mineralization rates during puberty.

Few studies of the VDR polymorphisms have looked at calcium metabolism or long-term effects. We measured bone mineralization and calcium metabolic parameters longitudinally in a group of 99 adolescents. We found a significant relationship between calcium absorption and skeletal calcium accretion and the Fok1, but not other VDR or related, genetic polymorphisms. It seems that the Fok1 polymorphism directly affects bone mineralization during pubertal growth through an effect on calcium absorption. INTRODUCTION: There are few data regarding the relationship between genetic markers for low bone mass and changes in calcium metabolism in childhood or adolescence. We sought to identify the effects of polymorphisms of the vitamin D receptor (VDR) on calcium and bone mineral metabolism in a longitudinal study of pubertal adolescents. MATERIALS AND METHODS: Adolescents (n = 99) received comprehensive stable isotope studies of calcium absorption, bone calcium kinetics, and bone mineralization. Studies were repeated 12 months later. Polymorphisms of putative genetic markers were determined and related to bone mineralization and calcium metabolic finding. Results were analyzed by ANOVA in which changes over time were determined using the initial value as a covariate. RESULTS: Polymorphisms of the Fok1 gene of the VDR were significantly related to calcium absorption (p = 0.008) and whole body BMC (p = 0.03) and BMD (p = 0.006). The Fok1 effect on whole body BMD was significant for those with Ca intake >800 mg/day (p < 0.001), whereas for those with Ca intake < or = 800 mg/day, the Fok1 genotype did not have a significant effect on whole body BMD (p = 0.40). The Fok1 genotype was significantly related to the changes during the year in whole body calcium accretion, with the ff genotype having a 63 +/- 20 mg/day deficit compared with the FF genotype (p = 0.008). CONCLUSIONS: The Fok1 polymorphism of the VDR receptor seems to directly affect bone mineral accretion during pubertal growth through an effect on calcium absorption. The relationship between different genetic polymorphisms and bone mineral metabolism may vary by life stage as well as diet.     

Association of urokinase gene 3'-UTR polymorphism with calcium oxalate nephrolithiasis

PURPOSE: Urokinase might play a role in the formation of kidney stones. The aim of this study was to investigate the role of the urokinase gene in calcium oxalate nephrolithiasis. SUBJECTS AND METHODS: A control group of 150 healthy individuals having no history of stone formation (mean age 40 +/- 11.5 years) and a group of 130 patients (mean age 40.5 +/- 10.5 years) with recurrent calcium oxalate stones were examined. The C/T polymorphism of the urokinase gene was detected using polymerase chain reaction (PCR)-based restriction analysis. RESULTS: A marginally significant difference (P = 0.035) was found in the distribution of the urokinase gene 3' untranslated region (UTR) C/T polymorphism between patients with stones and controls. The odds ratio for the risk of the T allele in stone patients was 1.006 (95% CI 0.63-1.62). CONCLUSION: The T allele of 3' UTR of the urokinase gene may not be associated with a higher risk of stone formation.     

Association of vitamin D receptor gene Taq I polymorphism with recurrent urolithiasis in children

OBJECTIVE: Urolithiasis has a strong familial component. However, to date, no specific genetic abnormality has been identified. It has been reported that allelic variation in the vitamin D receptor (VDR) gene may affect calcium absorption and excretion. Urolithiasis is a multifactorial disease in which both genetic and environmental factors have an effect on onset and severity of disease. In the present study, the role of Taq I polymorphism of vitamin D receptor gene in urolithiasis was studied. METHODS: Eighty children with calcium stone disease (40 with single episode of stone disease and 40 with recurrence) and 40 controls were enrolled. Polymorphic sites were amplified by polymerase chain reaction, digested with Taq I restriction enzymes and analyzed by gel electrophoresis. Allelic or genotypic frequencies were calculated and associations between them and the presence of hypercalciuria, family history and stone recurrence were evaluated. RESULTS: Incidence of Taq I tt genotypes was significantly higher in patients with recurrent calcium-stone disease compared to the controls. In addition, the frequency of the 't' allele was higher in recurrent calcium-stone formers. Taq I t allele was found to be associated with increased risk of recurrence. No association between Taq I polymorphism and a positive family history was found in the present study. The frequency of hypercalciuria was higher in patients with the 'tt' genotype. CONCLUSION: Taq I t allele of the VDR gene may be a risk factor for severe urolithiasis and recurrent stone disease.