Search Results (84)

Background/aim: Vitamin D (VitD) has been implicated in neuroprotection, yet its role in Parkinson’s disease (PD) remains unclear. This systematic review and meta-analysis aimed to evaluate the association between VitD status, supplementation, and vitamin D receptor (VDR) gene polymorphisms with PD risk and outcomes. Methodology: Following PRISMA guidelines, we searched PubMed, Scopus, and Google Scholar through August 2025 for observational studies, clinical trials, and genetic association studies. Primary outcomes included serum VitD levels in PD versus healthy controls (HCs), prevalence of VitD insufficiency/deficiency, and effects of VitD supplementation on motor symptoms. Secondary outcomes assessed associations between VDR polymorphisms and PD susceptibility. Data were synthesized using random- and fixed-effects models, with heterogeneity and publication bias evaluated. PROSPERO (CRD420251133875). Results: Sixty-three studies (n ≈ 10,700 participants) met inclusion criteria. PD patients exhibited significantly lower VitD levels (SMD = −0.46; 95% CI: −0.51 to −0.41) and higher odds of insufficiency (OR = 1.52) and deficiency (OR = 2.20) compared to HC. Cohort data suggested sufficient VitD may reduce PD risk (HR = 0.83). Supplementation yielded modest, non-significant improvements in motor outcomes. Among 20 genetic studies, FokI (rs2228570) was most consistently associated with PD, while other VDR SNPs showed variable or null associations. Conclusions: VitD deficiency is common in PD and may influence disease risk and motor function. Current evidence indicates limited benefit of supplementation for motor outcomes, and genetic associations remain inconsistent. Full article

Introduction: Vitamin D is involved in numerous processes and is obtained both exogenously and endogenously. Its active form is 1,25-dihydroxycholecalciferol, which exerts its biological effects via the vitamin D receptor (VDR). The main factors influencing VDR density are polymorphisms of the VDR gene, which may affect, e.g., gene mRNA stability and also VDR gene expression. There are four main polymorphic sites within the gene, BsmI, ApaI, FokI and TaqI, and two polymorphisms related to the gene promoter: GATA and Cdx2. One of the functions of vitamin D is to modulate the immune system. It affects T lymphocytes, B lymphocytes and dendritic cells. Currently, vitamin D deficiency is a common global problem that is associated with an increased risk of autoimmune diseases, including Hashimoto’s thyroiditis. Numerous studies have demonstrated an association between low vitamin D levels and elevated thyroid-stimulating hormone (TSH) levels, and have also proven the existence of a negative correlation between vitamin D levels andanti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibody titers. Review objectives and a concise summary of the methodology: The review aims to analyze studies examining the relationship between specific VDR polymorphisms, vitamin D levels, and the development of various diseases, with a particular emphasis on Hashimoto’s thyroiditis. This review is based on original and review articles written in English published between March 2018–November 2024 searched primarily in the PubMed, and additionally in Google Scholar databases. A narrative review of the literature was conducted. Conclusions: The presence of specific VDR polymorphisms influences the effectiveness of vitamin D supplementation, but the role of supplementation in the prevention of autoimmune diseases has not been definitively confirmed. To date, studies have primarily involved relatively small groups of patients with significant population heterogeneity, with case–control investigations being the most common. Therefore, further research on larger, more homogeneous groups is recommended to achieve more standardized results. Additionally, the influence of epigenetic factors modulating VDR activity and its interactions with the environmental factors is also important. Full article

Background/Objectives: We aimed to investigate the association between VDR gene variants and vitamin D levels in elite male power athletes of Kazakhstan. Methods: We recruited 92 elite male power athletes of Kazakhstan. Concentrations of serum 25(OH)D were measured with the Access 25(OH) Vitamin D Total Assay on the Unicel Dxl 800 Access Immunoassay System. Gene polymorphisms were determined by a real-time polymerase chain reaction (RT-PCR) allelic discrimination assay using TaqMan™ probes. Results: Vitamin D insufficiency was registered in 63% of athletes. Age (χ² = 6.83, p < 0.01), BMI (χ² = 6.83, p < 0.01), and sport experience (χ² = 4.44, p < 0.04) showed a statistically significant association with vitamin D insufficiency and deficiency (age, χ² = 7.93, p < 0.01; BMI, χ² = 5.11, p < 0.03; sport experience, χ² = 6.19, p = 0.01). The A/A genotype of the VDR FokI polymorphism (rs2228570) showed a strong correlation with vitamin D insufficiency (G/G-G/A vs. A/A, OR = 9.25, 95% CI = 2.01–42.51, p < 0.01) but not deficiency. Conclusions: Our study reveals a significant prevalence of vitamin D insufficiency and deficiency among elite male power athletes of Kazakhstan. Age, BMI, and sport experience are essential factors in developing personalized strategies to address vitamin D insufficiency. The A/A genotype of the VDR FokI polymorphism can be used as a potential biomarker for vitamin D inadequacy in elite male power athletes of Kazakhstan. Full article

Introduction: Dry Eye Syndrome (DES) is a multifactorial disorder of the ocular surface, characterized by complex interactions between environmental factors, immune dysregulation, and potential genetic predispositions. Vitamin D deficiency, known for its immunomodulatory properties, has increasingly been implicated in the pathogenesis of DES; however, the underlying mechanisms remain insufficiently elucidated. Of particular interest is the vitamin D receptor (VDR) gene, whose polymorphisms may influence the bioavailability and biological activity of vitamin D. Objective: The aim of this study was to investigate the association between serum 25-hydroxyvitamin D [25(OH)D₃] levels and selected polymorphisms in the VDR gene (Taq, Fok, Apa, and Bsm) in patients with DES and to analyze their potential clinical and genetic interactions. Methods: This prospective observational study included 60 patients with a confirmed diagnosis of DES. Serum 25(OH)D₃ levels were measured, and genotyping of four VDR single-nucleotide polymorphisms (SNPs) was performed using PCR followed by restriction fragment length polymorphism analysis. Genotype distributions were assessed in relation to vitamin D status using appropriate statistical tests and Hardy–Weinberg equilibrium analysis. Results: Over 85% of patients exhibited insufficient or deficient vitamin D levels. Among the analyzed SNPs, only the ApaI polymorphism (rs7975232) showed a statistically significant association with vitamin D status (p = 0.0384), with the homozygous AA genotype being more prevalent among patients with hypovitaminosis. The remaining polymorphisms (TaqI, FokI, BsmI) did not reach statistical significance; however, potential trends were observed that may warrant further investigation in larger cohorts. Conclusion: The findings suggest a potential role for VDR gene variability in the regulation of systemic vitamin D levels in patients with DES. Identification of specific genotypes may contribute to the development of personalized diagnostic and therapeutic strategies, particularly for patients with treatment-resistant forms of the disease. These results support the integration of genetic biomarkers and nutritional parameters into modern ophthalmologic practice. Full article

Secondary metabolites, including alkaloids, flavonoids, and tannins, are crucial for human health, agriculture, and ecosystem functioning. Their synthesis is often species-specific, influenced by both genetic and environmental factors. The increasing demand for these compounds across various industries highlights the need for advancements in plant breeding and biotechnological approaches. Transcription activator-like effector nucleases (TALENs) have emerged as a powerful tool for precise genome editing, offering significant potential for enhancing the synthesis of secondary metabolites in plants. However, while plant genome editing technologies have advanced significantly, the application of TALENs in improving secondary metabolite production and expanding genetic diversity remains underexplored. Therefore, this review aims to provide a comprehensive analysis of TALEN-mediated genome editing in plants, focusing on their role in enhancing secondary metabolite biosynthetic pathways and improving genetic diversity. The mechanisms underlying TALENs are examined, including their ability to target specific genes involved in the synthesis of bioactive compounds, highlighting comparisons with other genome editing tools such as CRISPR/Cas9. This review further highlights key applications in medicinal plants, particularly the modification of pathways responsible for alkaloids, flavonoids, terpenoids, and phenolic compounds. Furthermore, the role of TALENs in inducing genetic variation, improving stress tolerance, and facilitating hybridization in plant breeding programs is highlighted. Recent advances, challenges, and limitations associated with using TALENs for enhancing secondary metabolite production are critically evaluated. In this review, gaps in current research are identified, particularly regarding the integration of TALENs with multi-omics technologies and synthetic biology approaches. The findings suggest that while underutilized, TALENs offer sustainable strategies for producing high-value secondary metabolites in medicinal plants. Future research should focus on optimizing TALEN systems for commercial applications and integrating them with advanced biotechnological platforms to enhance the yield and resilience of medicinal plants. Full article

Background: Vitamin D receptor (VDR) polymorphisms may influence immune regulation and musculoskeletal health, but their perioperative role is not well understood. This study investigated the rs2228570 (FokI) variant in relation to inflammatory, hematologic, and patient-reported outcomes in orthopedic patients. Methods: We genotyped 300 orthopedic patients and 200 healthy controls using real-time PCR. Regression models in patients adjusted for age and body mass index (BMI) examined associations between rs2228570 genotypes and laboratory as well as clinical outcomes. Results: The CC genotype (homozygous cytosine) was associated with higher white blood cell count (β = 0.52, p = 0.0435), higher lymphocyte count (β = 0.26, p = 0.00025), higher hemoglobin (β = 0.57, p = 0.00197), and higher hematocrit (β = 1.42, p = 0.01102). The TT genotype (homozygous thymine) was associated with higher C-reactive protein (β = 10.90, p = 0.00329), lower mean corpuscular volume (β = −1.63, p = 0.04909), and higher health-related quality of life assessed by the 36-Item Short-Form Health Survey (SF-36) (β = 6.31, p = 0.00009). Conclusions: The rs2228570 polymorphism in the VDR gene is associated with distinct perioperative inflammatory, hematologic, and patient-reported profiles. These findings support the potential clinical utility of VDR genotyping, in combination with routine laboratory tests, to refine perioperative risk stratification and guide personalized rehabilitation in orthopedic patients. Full article

Background and Objectives: Lumbar disc herniation (LDH) is influenced by genetic, mechanical, and behavioral factors, with genetic predisposition playing a key role. Vitamin D receptor (VDR) polymorphisms have been implicated in LDH susceptibility, warranting further investigation. This study aimed to assess the association between VDR polymorphisms (FokI, ApaI, and TaqI) and LDH risk through a systematic review, meta-analysis, and trial sequential analysis (TSA). Materials and Methods: A systematic literature search was conducted across PubMed, Web of Science, Scopus, Cochrane Library, and CNKI, up until 30 January 2025. A meta-analysis was performed using Review Manager 5.3, with odds ratios (ORs) and 95% confidence intervals (CIs), and heterogeneity assessed via the I² statistic. The publication bias and TSA were evaluated using CMA 3.0 and TSA software to ensure the reliability of the results. The FATHMM-XF method was applied to predict the functional effect of coding and non-coding polymorphisms. Results: From 79 records, 10 studies were entered into the meta-analysis. The meta-analysis results showed no significant association of FokI and ApaI polymorphisms with LDH, while TaqI exhibited a protective effect, particularly in Asian populations and larger studies. The subgroup analysis revealed significant ethnicity-specific associations for TaqI, with stronger effects observed in Asian compared to Caucasian individuals. The trial sequential analysis indicated that additional studies are required to confirm the findings for FokI, while the recessive model of TaqI polymorphism showed a near-sufficient sample size for reliable conclusions. Conclusions: The TaqI polymorphism, particularly the tt genotype, appears to have a protective effect against LDH, especially in Asian populations and larger studies. However, further large-scale, multi-ethnic research is needed to confirm these findings and explore underlying biological mechanisms. Full article

Vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) modulate vitamin D/VDR signaling, a key pathway in inflammatory bowel disease (IBD) pathogenesis. This study investigates how ApaI, BsmI, TaqI, and FokI SNPs affect IBD phenotype and progression. A total of 76 Crohn’s disease (CD) and 68 ulcerative colitis (UC) patients were genotyped. On initial bivariate analysis, the AA genotype of ApaI was accompanied by higher rates of penetrating (B3) CD (36.7% vs. 8.7%; p = 0.012). The FokI SNP was associated with disease location, with the ff genotype predisposing to CD and affecting the upper GI (36.4% vs. 7.7%; p = 0.044) or the colon (90.9% vs. 50.8%; p = 0.038). Moreover, patients harboring the ApaI A allele (AA/Aa) experienced higher rates of steroid-refractory or steroid-dependent CD. In multivariate analyses, the aa genotype showed a protective effect against hospitalization (aOR = 0.17; p = 0.013) in CD, whereas the TT genotype emerged as an independent risk factor (aOR = 4.79; p = 0.044). Moreover, the aa genotype was independently associated with a decreased risk of IBD-related surgery (aOR = 0.055; p = 0.014). VDR SNPs, particularly ApaI, influence disease phenotype, progression, and treatment response in CD. The aa genotype of ApaI appears to confer protection against adverse disease outcomes. Full article

Background/Objectives: Vitamin D helps the mineralization of bone, teeth, and other calcified tissues by regulating calcium–phosphate metabolism. The nuclear activation of the vitamin D receptor (VDR) gene is essential for the effectiveness of vitamin D. The main objective of this study is to determine the role of vitamin D levels and VDR gene variants in dental caries. Methods: This study included 128 3–6-year-old children who were divided into 64 caries-free and 64 carious children. Blood samples were taken, and serum 25-hydroxyvitamin D levels were measured. Intraoral examinations were performed to record dmft index values. Genetic testing was performed on 26 children to examine VDR gene variations. Relevant gene regions were amplified using PCR and sequenced via Sanger sequencing in a total of 13 caries-free and 13 carious children. Stats analyses included chi-square/trend tests to compare count data; Student’s T/Mann–Whitney U tests for two-group normally/non-normally distributed data; and the Kruskal–Wallis test for 3+ groups with non-normal data. Results: The results showed that vitamin D levels were relatively low in the caries group, but no statistically significant relationship was found between vitamin D levels and caries. No mutations were detected in the VDR gene in either group, and there was no significant difference observed in terms of the number of ApaI, TaqI, and FokI polymorphisms. Based on these findings, the use of prophylactic vitamin D supplements to prevent caries formation or development cannot be recommended. Conclusions: This study provides important insights into the relationship between vitamin D and dental caries and can contribute to the development of effective preventive strategies for oral and dental health. Full article

Preterm birth (PTB) forms a heterogeneous group with possible genetic predisposition. 25(OH)-vitamin D3 plays a significant role during implantation, placentation, and the maintenance of normal pregnancy. The aim of our research was to examine whether FokI, Cdx2, and ApaI VDR gene variants, as well as serum concentrations of 25-hydroxy25(OH)-vitamin D3 in women and their newborns, might be predisposing factors for idiopathic spontaneous preterm birth. The patient group consisted of 44 pairs of women with ISPTB and their children, and the control group consisted of 44 pairs of women who delivered at term and their children. At the time of delivery, peripheral blood was collected from every woman, and after newborn delivery, umbilical cord blood was collected. For genotyping of the rs2228570 C/T, rs11568820 G/A, and rs7975232 T/G SNPs, a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used. Serum concentrations of 25(OH)-vitamin D3 were determined using high-performance liquid chromatography (HPLC). There were no statistically significant differences in the frequencies of VDR genotypes and alleles between women with ISPTB and control women. There was a statistically significant difference in the distribution of VDR Cdx-2 (rs11568820) genotypes between preterm-born children and controls, with the GG genotype and G allele being more prevalent among patients than controls (p < 0.001). There were no statistically significant differences in mean values between women with ISPTB and control women, nor between preterm and full-term newborns, although the 25(OH)-vitamin D3 concentrations in preterm-born children were lower than in controls. Furthermore, there was a statistically significant correlation in 25(OH)-vitamin D3 concentrations between mothers and children both in the patient and in the control groups (b = 0.771, p < 0.001). The results of our study demonstrate a notable association between the VDR Cdx2 gene polymorphism and idiopathic spontaneous preterm birth (ISPTB) in a Caucasian population, but because of the small number of participants, further research is needed. Full article

Colorectal cancer (CRC) is a major public health problem worldwide, currently ranking third in cancer incidence and second in mortality. Multiple genes and environmental factors have been involved in the complex and multifactorial process of CRC carcinogenesis. VDR is an intracellular hormone receptor expressed in both normal epithelial and cancer colon cells at various levels. Several VDR gene polymorphisms, including FokI and BsmI, have been evaluated for their possible association with CRC susceptibility. The aim of our study was to investigate these two SNPs for the first time in Romanian CRC patients. FokI (rs228570 C>T) and BsmI (rs1544410 A>G) were genotyped by real-time polymerase chain reaction (RT-PCR) in 384-well plates using specific TaqMan predesigned probes on a ViiA™ 7 RT-PCR System. A total of 441 subjects (166 CRC patients and 275 healthy controls) were included. No statistically significant difference was observed between CRC patients and controls when we compared the wild-type genotype with heterozygous and mutant genotypes for both FokI (OR 0.85, 95% CI: 0.56–1.28; OR 0.95, 95% CI: 0.51–1.79, respectively) and BsmI (OR 0.97, 95% CI: 0.63–1.49; OR 1.10, 95% CI: 0.65–1.87, respectively) or in the dominant and recessive models. Also, we compared allele frequencies, and no correlation was found. Moreover, the association between these SNPs and the tumor site, TNM stage, and histological type was examined separately, and there was no statistically significant difference. In conclusion, our study did not show any association between FokI and BsmI SNPs and CRC susceptibility in a Romanian population. Further studies including a larger number of samples are needed to improve our knowledge regarding the influence of VDR polymorphism on CRC susceptibility. Full article

Background: Vitamin D, through the activation of its receptor (VDR), plays an immunomodulatory role in the gastrointestinal tract. Single-nucleotide polymorphisms (SNPs) in the VDR gene have been associated with Crohn’s disease (CD) risk, and patients carrying the TaqI polymorphism in this gene run a higher risk of developing a penetrating behavior. Aims: We analyzed the association of BsmI, ApaI, TaqI, and FokI SNPs in the VDR gene with the clinical characteristics of CD. Methods: Four polymorphisms identified in the VDR gene (BsmI, FokI, ApaI, and TaqI) were genotyped in blood samples from CD patients (n = 115) by using PCR-RFLP. The disease’s location and behavior and the presence of perianal fistulas were collected from each patient. Intestinal fibroblasts from ileal resections of CD patients (n = 10) were genotyped, and the expression of fibrotic and inflammatory markers was analyzed by RT-PCR. Results: The data reveal no association between any of the polymorphisms and CD risk. A strong linkage disequilibrium was detected between TaqI and both ApaI and BsmI, which in turn were strongly associated. Homozygosis or heterozygosis for the a allele of the ApaI SNP or b allele of the BsmI SNP was significantly associated with a lower risk of a penetrating behavior, while the aa genotype was associated with a lower risk of perianal fistulas. Fibroblasts carrying the aa genotype expressed lower levels of fibrotic and inflammatory markers. Conclusion: The aa genotype of the ApaI SNP in the VDR gene is associated with a lower risk of perianal fistulas in CD and a reduced expression of fibrotic and inflammatory markers in intestinal fibroblasts. Full article

Background: A possible role of vitamin D epimers and metabolites in the measurement and response to treatment of vitamin D has been reported recently. Furthermore, the influence of underlying vitamin D receptor (VDR) genetic polymorphisms which have been linked to diseases such as obesity remains unclear. We therefore aimed to examine the influence of vitamin D3 and calcium supplements on vitamin D epimer and metabolite concentrations in subjects with and those without vitamin D receptor (VDR) gene polymorphisms. Methods: A total of 277 participants who were part of a randomized intervention trial of vitamin D3 and calcium or a placebo for 6 months had clinical and anthropometric assessments. Blood samples were taken for measurements of vitamin D, epimers and metabolites of vitamin D, four vitamin D receptor gene polymorphism SNPs, namely, BsmI, FokI, TaqI, and ApaI, metabolic and inflammatory markers, and related biochemical variables. Repeated-measures analysis of variance was used to assess the between-group difference in cumulative changes in vitamin D epimers and metabolites at 6 months after adjusting for the presence of the 4 VDR genotypes and allele gene polymorphisms. Results: Overall, 277 participants, with a mean (±SD) age of 41 ± 12 and 204 (74%) of whom were female, were included in the study. We found no statistically significant differences in vitamin D metabolites or (epimers) between male and females or younger subjects compared to those over 40 years of age except in 7C4 BL (p < 0.05). There was a statistically significant difference in 1,25(OH)2D3 concentrations between subjects with and those without genotypes AG and the allele G SNP2_Taql VDR gene polymorphism. Vitamin D3 concentrations were also significantly lower in subjects with the CC SNP3_Apal gene polymorphism compared to those without the CC SNP3 gene. No statistically significant effects were seen on vitamin D epimers and metabolites concentration in response to supplements before or after adjusting for the presence of the 4 VDR genotypes and allele gene polymorphisms. Conclusions: The CC SNP3 gene had statistically significant influence on vitamin D3 levels. Vitamin D and/or calcium supplements, however, had no effects on vitamin D epimer and metabolite concentration before or after adjusting for the presence of the 4 VDR genotypes and alleles. Full article

Background and Objectives: Polycystic ovary syndrome (PCOS) is a frequent and complex multidisciplinary disorder. Data regarding the role of genes involved in vitamin D metabolism in PCOS are as-yet elusive but suggest an association of VDR (vitamin D receptor) and vitamin D levels with metabolic, endocrine and cutaneous manifestations. The aim of this study was to evaluate the association between VDR gene polymorphisms and cutaneous manifestations, to find a correlation between hormonal parameters, oxidative stress and skin manifestations in women with PCOS, and to determine the impact of VDR gene polymorphisms on these parameters. Materials and Methods: This case–control study included 39 controls and 46 women with PCOS, matched by age and BMI distribution. Acne, hirsutism, seborrhea, androgenetic alopecia, oxidative stress and androgen hormones were recorded. VDR gene polymorphisms ApaI, FokI and TaqI were examined by polymerase chain reaction restriction fragment length polymorphism, and the androgen hormone (total testosterone, DHEAS), SHBG and malondialdehyde levels were assessed. Results: The most frequent skin manifestations in PCOS cases were acne followed by seborrhea, hirsutism and androgenic alopecia. The VDR-FokI polymorphism CC genotype had a significant protective role in the odds of acne (OR = 0.11, 95% CI: [0.02, 0.70], p = 0.015, p-corrected = 0.040) and seborrhea (OR = 0.15, 95% CI: [0.03, 0.75], p = 0.019, p-corrected = 0.039). The results demonstrated a significant protective effect of the C allele on the odds of acne and seborrhea in PCOS cases. Moreover, the dominant genotype of VDR-TaqI could have a protective role against oxidative stress (lower MDA levels) compared to patients carrying the TT genotype. Conclusions: In summary, this is the first study to demonstrate that the FokI CC genotype may have a protective role against both acne and seborrhea in women with PCOS, while the VDR-TaqI dominant genotype is associated with diminished oxidative stress in PCOS patients. Full article

A total hip arthroplasty (THA) can improve quality of life, but loosening of the hip prosthesis is a complex problem in which vitamin D may also play a role. The Vitamin D Receptor (VDR) is involved in the response of cells to the action of vitamin D, and its genetic variability raises the question of whether individual differences could influence the risk of prosthesis loosening. The aim of this study was to investigate the relationship between VDR single nucleotide polymorphisms (SNPs) (ApaI, BsmI, FokI and TaqI) and the serum VDR and 25(OH)D levels in three groups of patients: (1) arthroscopy patients after THA without loosening of the prosthesis (CA—Control Arthroplasty), (2) patients after THA with loosened hip prostheses (L—Loosening) and (3) the control group (C—Control). Our results suggest that the genotypes tt of TaqI, BB of BsmI, and FF of FokI may influence the VDR effect in patients with loosened protheses. Our results showed that the ACAC haplotype (AtBF) was over two times more frequent in the L group than in CA + C: OR =2.35 [95% CI 1.44–3.83; p = 0.001]. There was no significant correlation between the VDR and serum 25(OH)D levels, but there were differences between studied groups. Full article