Vitamin D Receptor (VDR) Gene Polymorphisms Modify the Response to Vitamin D Supplementation: A Systematic Review and Meta-Analysis

The vitamin D receptor (VDR), a member of the nuclear receptor superfamily of transcriptional regulators, is crucial to calcitriol signalling. VDR is regulated by genetic and environmental factors and it is hypothesised that the response to vitamin D supplementation could be modulated by genetic variants in the VDR gene. The best studied polymorphisms in the VDR gene are Apal (rs7975232), BsmI (rs1544410), Taql (rs731236) and Fokl (rs10735810). We conducted a systematic review and meta-analysis to evaluate the response to vitamin D supplementation according to the BsmI, TaqI, ApaI and FokI polymorphisms. We included studies that analysed the relationship between the response to vitamin D supplementation and the genotypic distribution of these polymorphisms. We included eight studies that enrolled 1038 subjects. The results showed no significant association with the BsmI and ApaI polymorphisms (p = 0.081 and p = 0.63) and that the variant allele (Tt+tt) of the TaqI polymorphism and the FF genotype of the FokI variant were associated with a better response to vitamin D supplementation (p = 0.02 and p < 0.001). In conclusion, the TaqI and FokI polymorphisms could play a role in the modulation of the response to vitamin D supplementation, as they are associated with a better response to supplementation.

Daily Soy–Catfish–Anchovy–Rice (SCAR) Porridge Increases 25(OH)D Serum Levels in Tuberculosis Patients with Vitamin D Receptor Gene Polymorphisms

BACKGROUND: The presence of vitamin D receptor (VDR) polymorphism and high levels of inflammatory markers are predisposing factors indicating disease progression and malnutrition. To meet nutritional needs in maintaining nutritional status in tuberculosis patients with VDR gene polymorphisms (TaqI or FokI), food that is easily absorbed and high in vitamin D, calcium, and protein is needed. This study was conducted to determine whether high vitamin D and calcium porridge called soy–catfish–anchovy–rice (SCAR) porridge would increase 25(OH)D serum levels and other parameters, including calcium, albumin, high-sensivity C-reactive protein (hs-CRP), and blood glucose serum levels.METHODS: The study was a parallel, open, clinical trial. There were 22 subjects in the intervention (I) group who received 50 g of SCAR porridge once per day along with dietary counseling, and 21 subjects in the control (C) group who only received dietary counseling. All subjects with TC and CC (TaqI) or TC and CC (FokI) genotype were included in this study. The intervention lasted for 14 days, and the parameters such as 25(OH)D, calcium, albumin, hs-CRP, and blood glucose serum levels were assessed before and after intervention between groups.RESULTS: All subjects in both groups completed the study. After 14 days of intervention, there was a significant increase in 25(OH)D (p=0.01) and decrease in hs-CRP (p=0.02) serum levels in the I group, and no change was observed in the C group. There was no significant difference in albumin and blood glucose serum levels.CONCLUSION: The results show that 50 g of SCAR porridge per day for 14 days is an effective supplementation that can increase 25(OH)D and decrease hs-CRP serum levels in tuberculosis patients with VDR gene polymorphism.KEYWORDS: vitamin D, hs-CRP, polymorphism, porridge

Influence of VDR gene polymorphisms on the development and course of breast cancer

Annotation. Breast cancer is the most common cancer diagnosed in women. In the last 5 years, it has been diagnosed in 7.8 million women, and in 2020, 685,000 deaths from breast cancer were registered. The growing number of patients with this pathology and the cost of therapy creates a need to study new methods of diagnosis and treatment. Therefore, detailed attention is paid to genetic risk factors for cancer, in particular, the VDR gene and its polymorphisms ApaI, TaqI, BsmI and FokI. Therefore, the purpose of this review is to collect and analyze currently known information about these SNPs and their relationship to the development, course and effectiveness of breast cancer treatment. To do this, an extensive literature review was conducted using basic databases, which described the effect of vitamin D3 on the tumor process and found that VDR receptor dysfunction increases the risk of breast cancer and affects the sensitivity of patients to treatment, which proves the effect of polymorphisms. ApaI, TaqI, BsmI and FokI on the development of pathology. Therefore, the prospects for further research are to study the prognostic value of each polymorphism and develop new treatments for the disease.

Vitamin D receptor gene polymorphisms and the effectiveness of assisted reproductive technology

Introduction. Vitamin D administration is recommended for women with vitamin D insufficiency, who are planning to undergo assisted reproductive treatment (ART). The action of the active form of vitamin D is mediated through its vitamin D receptor (VDR). The presence of VDR in the cells and tissues of the female reproductive system suggests that vitamin D plays an important role in human reproduction. However, the effect of VDR gene polymorphisms on human reproduction has not been adequately studied.Aim. To assess the effect of VDR gene polymorphisms on the folliculogenesis, embryogenesis and clinical outcomes of assisted reproduction programs.Materials and methods. The cross-sectional study included 300 patients without complications during the assisted reproduction cycle. The number of follicles, oocyte-cumulus complexes, mature and immature oocytes, the presence of oocyte dysmorphisms, number of zygotes, fertilization rate, and the number of obtained blastocysts were evaluated. The determination of three polymorphisms of the VDR gene (FokI – rs2228570, BsmI – rs1544410, TaqI – rs731236) was performed by real-time polymerase chain reaction.Results. The incidence of perivitelline space pathology of oocytes in FokI A/A genotype patients was 5.7%, in A/G genotype patients – 14.7%, in G/G genotype patients – 16.3% (p = 0.041 when comparing A/A genotype with A/G + G/G genotypes). Depending on the genotype, the pregnancy rate ranged from 38.5 to 52.8%, but no statistically significant differences were found.Conclusion. It was shown that the perivitelline space pathology of oocytes in the FokI A/G genotype patients is 2.6 times higher, and in the G/G genotype patients – 2.9 times higher than in the A/A genotype patients. However, there were no differences in pregnancy rate among patients with different genotypes of FokI, BsmI and TaqI gene polymorphisms of VDR.

Association of Vitamin D Receptor Gene Polymorphism with Type 2 Diabetes in the Northern Region of Saudi Arabian Population

Background: Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms are associated with type 2 diabetes mellitus (T2DM), However, its association with type 2 diabetes mellitus) is controversial and has not been established in different ethnic populations. Therefore, we aimed to evaluate the possible association between VDR gene polymorphisms (Fok1, Bsm1, and Taq1and Apa1) and T2DM patients in Saudi Arabia. Methods: 100 patients with T2DM and 100 healthy age-matched control subjects were enrolled. Fasting blood glucose, lipids profile and HbA1c were measured by autoanalyzer. The circulatory level of 25 hydroxyvitamin D [25(OH)D] was measured by immunochemiluminance. VDR gene polymorphisms detection has been done by polymerase chain reaction through restriction fragment length polymorphism (PCR-RFLP) method. Results: Our study has shown lower levels of 25(OH) D in patients with T2DM (in comparison with control subjects (44.65 ± 7.19), p < 0.00. There were statistically significant differences between patients with type 2 diabetes and controls regarding the distribution of FokI and Taq1 genotypes and alleles (p<0.004 and p<0.04) and nonsignificant differences regarding Bsm1genotpes and allele. Conclusions: Vitamin D deficiency is prevalent in T2DM patients in Saudi Arabia. An association was found between VDR FokI and Taq1 gene polymorphism and susceptibility to T2DM in Saudi Arabian patients.

Urinary tract infections and vitamin D: prospects for use in prevention and treatment

Urinary tract infections are a common global problem among physicians of various specialties, including therapists, pediatricians, nephrologists and urologists. Today UTI is one of the leading bacterial infections in both adult and child populations. The main type of therapy and prevention of recurrent UTI is the use of drugs with an antibacterial effect (antibiotics, uroseptics). An urgent problem in modern medical practice is the increasing antibiotic resistance, which requires the development of new approaches to therapy and prevention, including UTI. In recent years, special attention has been paid to the study of vitamin D receptor (VDR) gene polymorphisms as a possible risk factor determining the predisposition to a number of infectious and noninfectious diseases. More than 200 polymorphisms of the VDR gene have been identified, four of which – FokI, BsmI, ApaI, and TaqI – are particularly common. Different VDR alleles can cause small changes in receptor function, which can affect resistance or susceptibility to a particular infection. The review presents data from modern studies demonstrating the relationship between vitamin D supply and development, the frequency of recurrence and the nature of the course of UTI. In one study, vitamin D has been shown to enhance the cathelicidin-mediated antibacterial action of bladder epithelial cells. It also demonstrated the currently known defense mechanisms of vitamin D against urinary tract infections, including its effect on components of the innate immune system.

Vitamin D Receptor Gene Polymorphism as a Risk Factor for Chronic Periodontitis

Background: The aim of this study was to investigate vitamin D receptor (VDR) gene polymorphism as a risk factor associated with chronic periodontitis (CP) and to determine the effect of VDR gene polymorphism on phenotypic CP.Methods: This study is a case-control design that included 162 adults divided into two groups: patients with CP (case group) and patients without CP (control group). Venous blood and DNA were obtained from individual samples. The gene polymorphism was determined using Restricted Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR) and DNA sequencing to identify endonuclease restrictions in exon 9 (TaqI). The data were analyzed using an independent t-test and Fisher’s exact test. The odds ratio (OR) was used to calculate the risk of VDR gene polymorphism in CP. Results: VDR gene polymorphism was detected in patients with CP and a TT genotype (86.4%), Tt genotype (12.4%), and tt genotype (1.2%). The case group with TT and Tt genotypes had an OR of 12.5 (95% CI:1.6–99.8) of having CP compared to the control group (P<0.05).Conclusions: VDR gene polymorphisms (the TT and Tt genotypes) are risk factors associated with individual susceptibility to CP.

Vitamin D receptor gene polymorphisms and idiopathic Parkinson disease: an Egyptian study

Background Accumulating data have suggested that vitamin D receptor (VDR) gene is a pretender gene for vulnerability to Parkinson disease (PD). This study aimed to assess the relationship of VDR gene polymorphisms (FokI and ApaI) with PD. Fifty patients suffering from PD and 50 age- and sex-matched healthy controls were included. Unified Parkinson Disease Rating Scale (UPDRS) was done to assess disease severity. Genetic testing for VDR gene single nucleotide polymorphisms (FokI and ApaI) was done using real time polymerase chain reaction (PCR) technique. Results Concerning frequency of genes and alleles for vitamin D receptor gene polymorphisms (FokI and ApaI), no statistically significant difference was found between PD patients and controls. AC genotype was associated with younger age and younger age at onset of disease compared to CC and AA genotypes of ApaI gene polymorphisms. CC genotype was significantly positively correlated with fatigue and urine incontinence. VDR gene polymorphisms were not found to be independent predictors for severity of PD after adjustment for possible confounders. Conclusion VDR gene polymorphisms are related to the clinical manifestations rather than etiology or severity of idiopathic PD.