scholarly journals Perspectives of personalized approach to prevention and treatment of anticonvulsant-induced osteoporosis via action on vitamin D exchange and VDR expression

2021 ◽  
Vol 1 (2) ◽  
pp. 46-62
Author(s):  
E. A. Dontseva ◽  
V. V. Trefilova ◽  
T. E. Popova ◽  
M. M. Petrova ◽  
M. Al-Zamil
Keyword(s):  
Vitamin D ◽  
Back Pain ◽  
Chronic Back Pain ◽  
Association Studies ◽  
Single Nucleotide Variants ◽  
Vdr Gene ◽  
Vitamin D Metabolism ◽  
Vitamin D Receptors ◽  
Prevention And Treatment ◽  
Patients With Epilepsy

Anticonvulsant-induced osteoporosis (AIO) and associated pain syndromes and patient disabilities are an important interdisciplinary medical problem generated by various molecular, genetic and pathophysiological mechanisms. AIO are the most important pathological processes associated with chronic pain in adults with epilepsy. Standard approaches to their prevention and treatment do not always solve the problem of the progression of the pathological process and chronicity of AIO. This is the reason for the search for new personalized strategies for the prevention and treatment of AIO. Vitamin D metabolism, expression and specificity of vitamin D receptors (VDRs) may play a key role in the development of AIO and chronic back pain in patients with epilepsy. The aim of the study was to review publications on changes in the vitamin D system in patients with AIO. We searched for articles published in e-Library, PubMed, Oxford Press, Clinical Case, Springer, Elsevier, and Google Scholar. The search was carried out by key-words and their combinations. The role of vitamin D and VDR in the development of AIO and the chronicity of back pain has been demonstrated mainly in animal models and humans. Associative genetic studies have shown that single nucleotide variants (SNVs) of the VDR gene encoding VDR may be associated with the development of osteoporosis of the spine (including those associated with the intake of an anticonvulsants). The prospects for the use of vitamin D preparations for modulating the effect of anticonvulsants used to treat epilepsy are discussed. Genetic association studies of VDR gene SNVs are important for understanding the genetic predictors of AIO and chronic back pain in patients with epilepsy, as well as for developing new personalized pharmacotherapy strategies.

scholarly journals Vitamin D metabolism, sex hormones, and male reproductive function

Reproduction ◽  
2012 ◽  
Vol 144 (2) ◽  
pp. 135-152 ◽  
Author(s):  
Martin Blomberg Jensen
Keyword(s):  
Vitamin D ◽  
Association Studies ◽  
Reproductive Function ◽  
Hormone Production ◽  
Vitamin D Metabolism ◽  
Mediated Effects ◽  
Male Reproductive Function ◽  
Expression Studies ◽  
Metabolizing Enzyme ◽  
And Function

The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function. The VD receptor (VDR) and the VD metabolizing enzyme expression studies documented the presence of this system in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both systemic and local VD metabolism may influence male reproductive function. However, it is still debated which cell is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses mechanistic and association studies conducted in animals and humans. The reviewed evidence suggests some effects of VD on estrogen and testosterone biosynthesis and implicates involvement of both systemic and local VD metabolism in the regulation of male fertility potential.

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.

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.

scholarly journals A modern perspective of antiepileptic drugs effect on Vitamin D rate (reference data and clinical case)

2020 ◽  
Vol 10 (4) ◽  
pp. 193-197
Author(s):  
V.V. Povoroznyuk ◽  
Н.S. Dubetska ◽  
N.V. Zaverukha
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Antiepileptic Drugs ◽  
Sodium Valproate ◽  
Clinical Case ◽  
Young Patients ◽  
Systemic Review ◽  
Mineral Density ◽  
Vitamin D Metabolism ◽  
Patients With Epilepsy

This article presents a clinical case of the antiepileptic drug effect on the Vitamin D rate (namely, the patient has been taking Sodium Valproate for a long time) and new data from the foreign publications on this problem. It is known that there is a list of drugs that adversely affect the Vitamin D metabolism. In particular, the drugs reducing the Vitamin D absorption include drugs for the treatment of epilepsy. Antiepileptic drugs are drugs of va­rious origins that are used to prevent or reduce seizures, their corresponding conditions (loss or impairment of consciousness, behavioral and autonomic disorders, etc.), which are observed with recurrent seizures of various forms of epilepsy. The widespread use of these drugs in medical practice requires a detailed study of possible side effects of these drugs and their timely correction, as foreign sources indicate that antiepileptic drugs increase Vitamin D deficiency and worsen the symptoms of proximal myopathy, requiring mandatory medical correction; patients with epilepsy are deficient in vitamin D; сhronic Valproate therapy is associated with lower bone mineral density in young patients with epilepsy. This clinical case showed how a long-term use of Sodium Valproate led to the development of secondary systemic osteoporosis and Vitamin D deficiency, as evidenced by the results of laboratory and instrumental studies, and the discontinued antiepileptic drugs along with Vitamin D supplementation improved the general health of the patient and Vitamin D blood rates. Based on the systemic review and our own observations, it has been conclu­ded that epilepsy patients taking antiepileptic drugs should be gi­ven Vitamin D supplements to prevent the development of osteoporosis and Vitamin D deficiency.

scholarly journals Association of Vitamin D Metabolism Gene Polymorphisms with Autoimmunity: Evidence in Population Genetic Studies

2020 ◽  
Vol 21 (24) ◽  
pp. 9626
Author(s):  
Adolfo I. Ruiz-Ballesteros ◽  
Mónica R. Meza-Meza ◽  
Barbara Vizmanos-Lamotte ◽  
Isela Parra-Rojas ◽  
Ulises de la Cruz-Mosso
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Lupus Erythematosus ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Serum Levels ◽  
Nucleotide Polymorphisms ◽  
Vitamin D Metabolism ◽  
Single Nucleotide ◽  
High Prevalence

A high prevalence of vitamin D (calcidiol) serum deficiency has been described in several autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (AR), and systemic lupus erythematosus (SLE). Vitamin D is a potent immunonutrient that through its main metabolite calcitriol, regulates the immunomodulation of macrophages, dendritic cells, T and B lymphocytes, which express the vitamin D receptor (VDR), and they produce and respond to calcitriol. Genetic association studies have shown that up to 65% of vitamin D serum variance may be explained due to genetic background. The 90% of genetic variability takes place in the form of single nucleotide polymorphisms (SNPs), and SNPs in genes related to vitamin D metabolism have been linked to influence the calcidiol serum levels, such as in the vitamin D binding protein (VDBP; rs2282679 GC), 25-hydroxylase (rs10751657 CYP2R1), 1α-hydroxylase (rs10877012, CYP27B1) and the vitamin D receptor (FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) VDR). Therefore, the aim of this comprehensive literature review was to discuss the current findings of functional SNPs in GC, CYP2R1, CYP27B1, and VDR associated to genetic risk, and the most common clinical features of MS, RA, and SLE.

scholarly journals About the possible mechanisms of calcitriol influence on the development of preeclampsia in pregnant women

2019 ◽  
pp. 53-62
Author(s):  
G. S. Manasova ◽  
A. A. Zelinsky ◽  
N. V. Didenkul ◽  
N. V. Kuzmin ◽  
S. V. Derishov
Keyword(s):  
Vitamin D ◽  
Pregnant Women ◽  
Regulatory System ◽  
The Body ◽  
Vitamin D Receptors ◽  
Pathogenetic Mechanisms ◽  
New Methods ◽  
New Directions ◽  
Prevention And Treatment ◽  
Skeletal Effects

Preeclampsia (PE) of pregnant women remains one of the most important current problems of modern obstetrics. Despite various theories about the pathogenetic mechanisms of its development, new directions in the studying of this problem are continued to emerge. One of the promising areas of researches are works that  devoted to the studying of the vitamin D (VD) role in the genesis of PE, which were appeared due to the discovery of the "non-classical" and "extra-skeletal" effects of calcitriol. It is known now that the regulatory system, which is characterized by vitamin D receptors (VDR), is functioning in at least 38 organs and tissues of the body and controls more than 2200 genes. The VD – VDR system is able to specifically respond to the effects of calcitriol by its participation in angiogenesis, in the immune system and in the most important metabolic processes of the body. The presence of vitamin D receptors directly in the reproductive system and in the placenta allows to redefining of its role in the gestational process, particularly in the development of PE in pregnant women. This direction of research is important not only for understanding some aspects of the pathogenetic mechanisms of PE development, but it`s also the possibility of developing new methods for the prevention and treatment of this complication of pregnancy.

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.

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