scholarly journals Genetic variants of calcium and vitamin D metabolism in kidney stone disease

2019 ◽  
Author(s):  
Sarah A. Howles ◽  
Akira Wiberg ◽  
Michelle Goldsworthy ◽  
Asha L. Bayliss ◽  
Emily Grout ◽  
...  
Keyword(s):  
Vitamin D ◽  
Genetic Variants ◽  
Kidney Stone ◽  
Association Studies ◽  
Stone Disease ◽  
Calcium Excretion ◽  
Genome Wide Association Studies ◽  
Vitamin D Metabolism ◽  
Kidney Stone Disease

Kidney stone disease (nephrolithiasis) is a major clinical and economic health burden1,2 with a heritability of ~45-60%3. To identify genetic variants associated with nephrolithiasis we performed genome-wide association studies (GWAS) and meta-analysis in British and Japanese populations, including 12,123 nephrolithiasis cases and 416,928 controls. Twenty loci associated with nephrolithiasis were identified, ten of which are novel. A novel CYP24A1 locus is predicted to affect vitamin D metabolism and five loci, DGKD, DGKH, WDR72, GPIC1, and BCR, are predicted to influence calcium-sensing receptor (CaSR) signaling. In a validation cohort of nephrolithiasis patients the CYP24A1-associated locus correlated with serum calcium concentration and number of kidney stone episodes, and the DGKD-associated locus correlated with urinary calcium excretion. Moreover, DGKD knockdown impaired CaSR-signal transduction in vitro, an effect that was rectifiable with the calcimimetic cinacalcet. Our findings indicate that genotyping may inform risk of incident kidney stone disease prior to vitamin D supplementation and facilitate precision-medicine approaches, by targeting CaSR-signaling or vitamin D activation pathways in patients with recurrent kidney stones.

scholarly journals Genetic variants of calcium and vitamin D metabolism in kidney stone disease

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sarah A. Howles ◽  
Akira Wiberg ◽  
Michelle Goldsworthy ◽  
Asha L. Bayliss ◽  
Anna K. Gluck ◽  
...  
Keyword(s):  
Vitamin D ◽  
Kidney Stone ◽  
Association Studies ◽  
Vitamin D Supplementation ◽  
Stone Disease ◽  
Calcium Excretion ◽  
Genome Wide Association Studies ◽  
Vitamin D Metabolism ◽  
Kidney Stone Disease

AbstractKidney stone disease (nephrolithiasis) is a major clinical and economic health burden with a heritability of ~45–60%. We present genome-wide association studies in British and Japanese populations and a trans-ethnic meta-analysis that include 12,123 cases and 417,378 controls, and identify 20 nephrolithiasis-associated loci, seven of which are previously unreported. A CYP24A1 locus is predicted to affect vitamin D metabolism and five loci, DGKD, DGKH, WDR72, GPIC1, and BCR, are predicted to influence calcium-sensing receptor (CaSR) signaling. In a validation cohort of only nephrolithiasis patients, the CYP24A1-associated locus correlates with serum calcium concentration and a number of nephrolithiasis episodes while the DGKD-associated locus correlates with urinary calcium excretion. In vitro, DGKD knockdown impairs CaSR-signal transduction, an effect rectified with the calcimimetic cinacalcet. Our findings indicate that studies of genotype-guided precision-medicine approaches, including withholding vitamin D supplementation and targeting vitamin D activation or CaSR-signaling pathways in patients with recurrent kidney stones, are warranted.

Genetics of common complex kidney stone disease: insights from genome-wide association studies

Urolithiasis ◽  
2018 ◽  
Vol 47 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Runolfur Palsson ◽  
Olafur S. Indridason ◽  
Vidar O. Edvardsson ◽  
Asmundur Oddsson
Keyword(s):  
Kidney Stone ◽  
Association Studies ◽  
Stone Disease ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Kidney Stone Disease ◽  
Genome Wide

scholarly journals Calcium and Vitamin D Supplementation and Their Association with Kidney Stone Disease: A Narrative Review

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4363
Author(s):  
Matteo Bargagli ◽  
Pietro Manuel Ferraro ◽  
Matteo Vittori ◽  
Gianmarco Lombardi ◽  
Giovanni Gambaro ◽  
...  
Keyword(s):  
Vitamin D ◽  
Kidney Stone ◽  
Stone Formation ◽  
Vitamin D Supplementation ◽  
Stone Disease ◽  
Normal Body Mass Index ◽  
Calcium Excretion ◽  
Kidney Stone Disease ◽  
Low Calcium Diet ◽  
Stone Formers

Kidney stone disease is a multifactorial condition influenced by both genetic predisposition and environmental factors such as lifestyle and dietary habits. Although different monogenic polymorphisms have been proposed as playing a causal role for calcium nephrolithiasis, the prevalence of these mutations in the general population and their complete pathogenetic pathway is yet to be determined. General dietary advice for kidney stone formers includes elevated fluid intake, dietary restriction of sodium and animal proteins, avoidance of a low calcium diet, maintenance of a normal body mass index, and elevated intake of vegetables and fibers. Thus, balanced calcium consumption protects against the risk for kidney stones by reducing intestinal oxalate availability and its urinary excretion. However, calcium supplementation given between meals might increase urinary calcium excretion without the beneficial effect on oxalate. In kidney stone formers, circulating active vitamin D has been found to be increased, whereas higher plasma 25-hydroxycholecalciferol seems to be present only in hypercalciuric patients. The association between nutritional vitamin D supplements and the risk for stone formation is currently not completely understood. However, taken together, available evidence might suggest that vitamin D administration worsens the risk for stone formation in patients predisposed to hypercalciuria. In this review, we analyzed and discussed available literature on the effect of calcium and vitamin D supplementation on the risk for kidney stone formation.

scholarly journals Diet-Derived Antioxidants and Risk of Kidney Stone Disease: Results From the NHANES 2007–2018 and Mendelian Randomization Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhongyu Jian ◽  
Menghua Wang ◽  
Xi Jin ◽  
Hong Li ◽  
Kunjie Wang
Keyword(s):  
Vitamin C ◽  
Kidney Stone ◽  
Vitamin B6 ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Stone Disease ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Kidney Stone Disease ◽  
Stone Formers

We aimed to explore the associations between diet-derived antioxidants and kidney stone disease (KSD) risk in this study. We performed weighted multivariable-adjusted logistic regression to assess the associations between the six main diet-derived antioxidants and the risk of KSD by using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. Then, we used the Mendelian randomization (MR) approach to verify the causal relationships between circulating antioxidants levels and KSD risk. Genetic tools were extracted from published genome-wide association studies (GWAS). Summary data for KSD was from the FinnGen study and UK biobank. Inverse variance weighted (IVW) was the primary analysis. The 26,438 participants, including 2,543 stone formers, were included for analyses. There were no significant associations between retinol, vitamin B6, vitamin C, vitamin E, and lycopene intake with the risk of KSD across all the quartile categories. Similarly, pooled odds ratio (OR) for KSD risk in genetically predicted per unit change were 1.25 (95% CI: 0.39, 4.02; p = 0.712), 1.14 (95% CI: 0.84, 1.53; p = 0.400), 0.75 (95% CI: 0.52, 1.10; p = 0.141), 1.66 (95% CI: 0.80, 3.46; p = 0.178), 1.27 (95% CI: 0.29, 5.62; p = 0.756), and 0.92 (95% CI: 0.76, 1.12; p = 0.417) for retinol, β-carotene, vitamin B6, vitamin C, α-tocopherol, and lycopene, respectively. The above estimates were replicated in the secondary analyses using UK biobank data. Our study did not support a causal association between circulating antioxidants levels and KSD risk. However, these findings should be verified in larger sample-size MR due to the pleiotropy and other limitations.

Vitamin D and kidney stone disease

2013 ◽  
Vol 22 (4) ◽  
pp. 383-389 ◽  
Author(s):  
Jie Tang ◽  
Michel B. Chonchol
Keyword(s):  
Vitamin D ◽  
Kidney Stone ◽  
Stone Disease ◽  
Kidney Stone Disease

scholarly journals Genetic Variants Shaping Inter-individual Differences in Response to Dietary Intakes—A Narrative Review of the Case of Vitamins

2020 ◽  
Vol 7 ◽  
Author(s):  
Aikaterini Niforou ◽  
Valentini Konstantinidou ◽  
Androniki Naska
Keyword(s):  
Vitamin D ◽  
Vitamin C ◽  
Genetic Variants ◽  
Current Knowledge ◽  
Association Studies ◽  
Genetic Variations ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Dietary Intakes ◽  
Genes Encoding

Recent advances in the field of nutrigenetics have provided evidence on how genetic variations can impact the individuals' response to dietary intakes. An objective and reliable assessment of dietary exposures should rely on combinations of methodologies including frequency questionnaires, short-term recalls or records, together with biological samples to evaluate markers of intake or status and to identify genetic susceptibilities. In an attempt to present current knowledge on how genetic fingerprints contribute to an individual's nutritional status, we present a review of current literature describing associations between genetic variants and levels of well-established biomarkers of vitamin status in free-living and generally healthy individuals. Based on the outcomes of candidate gene, genome-wide-association studies and meta-analyses thereof, we have identified several single nucleotide polymorphisms (SNPs) involved in the vitamins' metabolic pathways. Polymorphisms in genes encoding proteins involved in vitamin metabolism and transport are reported to have an impact on vitamin D status; while genetic variants of vitamin D receptor were most frequently associated with health outcomes. Genetic variations that can influence vitamin E status include SNPs involved in its uptake and transport, such as in SCAR-B1 gene, and in lipoprotein metabolism. Variants of the genes encoding the sodium-dependent vitamin C transport proteins are greatly associated with the body's status on vitamin C. Regarding the vitamins of the B-complex, special reference is made to the widely studied variant in the MTHFR gene. Methodological attributes of genetic studies that may limit the comparability and interpretability of the findings are also discussed. Our understanding of how genes affect our responses to nutritional triggers will enhance our capacity to evaluate dietary exposure and design personalized nutrition programs to sustain health and prevent disease.

In vitro evidence of the promoting effect of testosterone in kidney stone disease: A proteomics approach and functional validation

2016 ◽  
Vol 144 ◽  
pp. 11-22 ◽  
Author(s):  
Channarong Changtong ◽  
Paleerath Peerapen ◽  
Supaporn Khamchun ◽  
Kedsarin Fong-ngern ◽  
Somchai Chutipongtanate ◽  
...  
Keyword(s):  
Kidney Stone ◽  
Stone Disease ◽  
Functional Validation ◽  
Promoting Effect ◽  
Kidney Stone Disease ◽  
Proteomics Approach

Genetic variants in m6A modification genes are associated with esophageal squamous-cell carcinoma in the Chinese population

2020 ◽  
Vol 41 (6) ◽  
pp. 761-768
Author(s):  
Nan Yang ◽  
Pingting Ying ◽  
Jianbo Tian ◽  
Xiaoyang Wang ◽  
Shufang Mei ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Variants ◽  
Association Studies ◽  
Valuable Insight ◽  
Genome Wide Association Studies ◽  
Cancer Occurrence

Abstract N 6-methyladenosine (m6A) is an abundant modification in RNAs that affects RNA metabolism, and it is reported to be closely related to cancer occurrence and metastasis. In this study, we focused on evaluating the associations between genetic variants in m6A modification genes and the risk of esophageal squamous-cell carcinoma (ESCC). By integrating data of our previous genome-wide association studies and the predictions of several annotation tools, we identified a single nucleotide polymorphism, rs2416282 in the promoter of YTHDC2, that was significantly associated with the susceptibility of ESCC (odds ratio = 0.84, 95% CI: 0.77–0.92, P = 2.81 × 10−4). Through further functional experiments in vitro, we demonstrated that rs2416282 regulated YTHDC2 expression. Knockdown of YTHDC2 substantially promoted the proliferation rate of ESCC cells by affecting several cancer-related signaling pathways. Our results suggested that rs2416282 contributed to ESCC risk by regulating YTHDC2 expression. This study provided us a valuable insight into the roles of genetic variants in m6A modification genes for ESCC susceptibility and may contribute to the prevention of this disease in the future.

Genetic and environmental determinants of 25-hydroxyvitamin D levels in multiple sclerosis

2014 ◽  
Vol 21 (11) ◽  
pp. 1414-1422 ◽  
Author(s):  
Julie H Laursen ◽  
Helle Bach Søndergaard ◽  
Anders Albrechtsen ◽  
Ruth Frikke-Schmidt ◽  
Nils Koch-Henriksen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Environmental Factors ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Protective Effects ◽  
Allelic Discrimination ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

Background: Evidence is accumulating supporting a beneficial effect of vitamin D in multiple sclerosis (MS). Genome-wide association studies (GWAS) have shown significant associations between 25-hydroxyvitamin D (25(OH)D) and single nucleotide polymorphisms (SNPs) in key genes in the vitamin D metabolism. Objective: To examine the association between 25(OH)D and six GWAS SNPs and environmental factors in 1497 MS patients. Methods: Blood samples and lifestyle questionnaires were collected between 2009 and 2012. Genotyping of GC-, CYP2R1- and NADSYN1-SNPs was performed by TaqMan allelic discrimination (Life Technologies). Results: We found significant associations between 25(OH)D and SNPs in GC (rs7041, p = 0.01 and rs2282679, p = 0.03) and CYP2R1 (rs10741657, p =1.8 × 10−4). Season of blood sampling (p = 2.8 × 10−31), sex ( p = 1.9 × 10−5), BMI ( p = 2.3 × 10−5), vitamin supplements ( p = 7.0 × 10−22), and fish intake ( p = 0.02) also had significant effects on 25(OH)D. Conclusion: In this cross-sectional study, we found significant effects of environmental factors and SNPs in GC and CYP2R1 on 25(OH)D in MS patients. Since 25(OH)D might have protective effects in MS, and vitamin D supply is a modifiable factor, it may be important to include this in the MS treatment regimen.

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