Vitamin D Receptor Gene Polymorphisms Research Articles

Associations between vitamin D status, VDR gene polymorphisms and echocardiographic markers in Polish patients with cardiovascular disease.

Aim: This work was designed to investigate the associations between vitamin D metabolites, VDR gene polymorphismsand echocardiographic markers in a population of patients with cardiovascular disease. Methods: Echocardiographic markers for 42 patients were determined with tissue Doppler techniques. PCR-restriction fragment length polymorphismanalysisidentified genetic variants ApaI, TaqI, BsmI and FokI. A validated UHPLC-MS/MS methoddetermined vitamin D metabolites. Results: Patients with the ApaI-GT genotype exhibited a lower pressure gradient across the aortic valve than ApaI-TT carriers. BMI, ApaI-GT, TaqI-TC, aortic arch diameterand maximal pressure gradient were significant univariate predictors of hypertension. Conclusion: A potential link existsbetween VDR gene polymorphisms and cardiovascular function.

Vitamin D Status, VDR, and TLR Polymorphisms and Pulmonary Tuberculosis Epidemiology in Kazakhstan.

Tuberculosis (TB) and vitamin D deficiency remain major public health problems in Kazakhstan. Due to the high incidence of pulmonary tuberculosis in the country and based on the importance of vitamin D in the modulation of the immune response and the association of its deficiency with many health conditions, the aim of our research was to study the vitamin D status, VDR and TLR gene polymorphisms, and pulmonary tuberculosis epidemiology in Kazakhstan. A case-control study included 411 individuals diagnosed with pulmonary TB and 686 controls with no family history of pulmonary tuberculosis. Concentrations of serum vitamin D (25-(OH)D) levels were measured by electrochemiluminescence immunoassay. The gene polymorphisms were determined by real-time polymerase chain reaction (PCR) allelic discrimination assay using TaqMan probes. The association between the risk of pulmonary TB and polymorphisms was evaluated using multimodal logistic regression and assessed with the ORs, corresponding to 95% Cis, and the significance level was determined as p < 0.05. 1097 individuals were recruited from 3 different regions of Kazakhstan. Biochemical data showed vitamin D deficiency (25-(OH)D < 20 ng/mL) was present in both groups, with the case group accounting for almost 95% and 43.7% in controls. Epidemiological data revealed that socioeconomic factors such as BMI < 25 kg/m2 (p < 0.001), employment (p < 0.001), diabetes (p < 0.001), and vitamin D deficiency (p < 0.001) were statistically different between case and control groups. Logistic regression analysis, adjusted by sex, age, BMI, residence, employment, smoking, alcohol consumption, and diabetes, showed that T/T polymorphism of the VDR gene (rs1544410, OR = 1.97, 95% CI: 1.04-3.72, p = 0.03) and A/A polymorphism of the TLR8 gene (rs3764880, OR = 2.44, 95% CI: 1.20-4.98, p = 0.01) were associated with a high risk of developing pulmonary tuberculosis. Vitamin D deficiency remains prevalent in our study cohort and is associated with TB progression. Socioeconomic determinants such as unemployment, BMI under 25 kg/m2, and diabetes are the main risk factors for the development of pulmonary TB in our study. A/A polymorphism of TLR8 (rs3764880) and T/T polymorphism (BsmI, rs1544410) of VDR genes may act as biomarkers for pulmonary tuberculosis in the Kazakh population.

The Association of Vitamin D Receptor Gene Polymorphisms with Vitamin D, Total IgE, and Blood Eosinophils in Patients with Atopy.

In order to improve the control of atopic diseases, it is important to clarify the pathogenesis of atopy and identify its various triggers. Single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene (VDR) may impact atopy. The aim of this study was to investigate the possible associations between VDR SNPs and vitamin D, total IgE, and eosinophils in atopy. In total, 203 adults, including 122 patients with atopic diseases (45 with atopic dermatitis, 77 with allergic asthma) and 81 healthy controls, were involved in the study. The blood eosinophil count was determined with an automated hematology analyzer. Vitamin D and total immunoglobulin E (IgE) levels were evaluated using the ELISA method. Polymorphisms in the VDR gene were analyzed with real-time PCR using TaqMan probes. We analyzed six VDR single nucleotide polymorphisms and found a significant association between VDR rs731236 GG genotype and normal vitamin D levels in atopic patients and healthy subjects (OR 11.33; 95% CI: 1.049-122.388 and OR 4.04; 95% CI: 1.117-14.588, respectively, p < 0.05). Additionally, the study results revealed a significant relationship between the VDR rs2228570 GG genotype and normal vitamin D levels in patients with atopy and healthy subjects (OR 3.80; 95% CI: 1.190-12.134 and OR 2.09; 95% CI: 1.044-4.194, respectively, p < 0.05). The rs2228570 allele A was associated with decreased vitamin D levels in patients with atopy and healthy subjects (OR 0.28; 95% CI: 0.098-0.804 and OR 0.229; 95% CI: 0.069-0.761, respectively, p < 0.05). The VDR rs3847987 genotypes AA and AC were significantly associated with normal vitamin D levels in healthy subjects (OR 35.99; 95% CI: 6.401-202.446 and OR 4.72; 95% CI: 1.489-15.007, respectively, p < 0.05). In addition, a decreased amount of vitamin D was associated with atopic diseases such as atopic dermatitis and allergic asthma (OR 0.49; 95% CI: 0.439-1.308 and OR 0.58; 95% CI: 0.372-0.908, respectively, p < 0.05). The rs11168293 allele T was associated with the normal range of total IgE in atopy (OR 2.366; 95% CI: 1.133-5.027; p < 0.05). Significant associations were found between VDR rs731263 allele G, rs11168293 allele G, and increased blood eosinophil levels in patients with atopy (OR 0.319; 95% CI: 0.163-0.934 and OR 0.323; 95% CI: 0.112-0.935, respectively, p < 0.05). A decreased vitamin D level showed a significant relationship with atopic diseases (atopic dermatitis and allergic asthma). The association between the VDR gene polymorphisms rs2228570, rs731236, and rs11168293 and vitamin D, total IgE, and blood eosinophils in patients with atopy suggested that VDR polymorphisms and the vitamin D level should be considered when examining the factors associated with atopy.

BMP6 and VDR gene polymorphisms are associated with osteonecrosis in a sickle cell anaemia cohort.

The occurrence and severity of osteonecrosis in sickle cell anaemia (SCA) vary due to risk factors, including genetic modifiers. Bone morphogenetic proteins (BMPs), particularly BMP6, and the vitamin D receptor (VDR) play key roles in cartilage and bone metabolism, making them potential contributors to orthopaedic outcomes in SCA. Here, we evaluated the association of polymorphisms in BMP6 (rs3812163, rs270393 and rs449853) and VDR (FokI rs2228570 and Cdx2 rs11568820) genes with osteonecrosis risk in a Brazilian SCA cohort. A total of 177 unrelated SCA patients were selected. The AA genotype of BMP6 rs3812163 was independently associated with a lower osteonecrosis risk (p = 0.015; odds ratio (OR): 0.38; 95% confidence interval (CI): 0.18-0.83) and with the long-term cumulative incidence of osteonecrosis (p = 0.029; hazard ratio: 0.56, 95% CI: 0.34-0.94). The VDR rs2228570 TT genotype was independently associated with a lower osteonecrosis risk (p = 0.039; OR: 0.14; 95% CI: 0.02-0.90). In summary, our results provide evidence that BMP6 rs3812163 and the VDR rs2228570 might be implicated in osteonecrosis pathophysiology in SCA and might help identify individuals at high risk.

Genetic Diversity in Bronchial Asthma Susceptibility: Exploring the Role of Vitamin D Receptor Gene Polymorphisms in Varied Geographic Contexts.

Bronchial asthma (BA) exhibits varying prevalence across global populations, prompting a comprehensive investigation into genetic and environmental determinants. Vitamin D is a potent immunomodulator capable of suppressing inflammatory signals in several cell types involved in the asthmatic response; it exerts effects on the immune system by binding to the nuclear vitamin D receptor (VDR). VDR gene genetic variations are affecting serum vitamin D levels with a possible role in the BA risk. The current study aimed to examine the complex interaction of various factors (genetic background, serum vitamin D levels, and geographic location) to identify differences in the influence of these factors on the susceptibility to asthma between populations at different latitudes. Focusing on Eastern European cohorts from Latvia and Lithuania and comparing them with published data on East Asian populations, we explore the impact of VDR gene polymorphisms on BA susceptibility. Genotyping four key VDR SNPs and assessing their association with 25-hydroxyvitamin D levels, our study unveils significant associations of the studied loci with the risk of asthma-both risk-reducing and increasing effects, differently distributed between Baltic and East Asian populations. The functional effects of in silico VDR gene genetic variations are also identified and discussed.

ApaI and Fok1 Variants of Vitamin D Receptor Gene Associated with Metabolic Syndrome Among Jordanian Women.

The association between vitamin D receptor (VDR) polymorphisms and metabolic syndrome (MS) remains debatable. The current study aimed to determine the correlation of VDR gene polymorphisms with MS among Jordanian women. This case-control study enrolled 100 women with MS and 100 age-matched women as control at Al-Hikma Modern Hospital in Jordan between January 2019 and January 2020. The levels of glycated hemoglobin, fasting glucose, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and 25-hydroxy vitamin D (25(OH)D) were determined from serum samples of all participants. DNA was extracted from whole blood samples, and VDR gene polymorphisms Apa1, Taq1, Bsm1, and Fok1 were analyzed by polymerase chain reaction and restriction fragment length polymorphism. There was a significant difference between MS patients and control in terms of body mass index (34.3±3.1 vs. 28.1±2.5), glycated hemoglobin (5.9±1.1 vs. 4.6±1.2), fasting blood glucose (6.4±1.6 vs. 5.2±1.4), and total cholesterol (6.5±1.2 vs. 5.3±1.8). The results also demonstrated a statistical difference in the number of MS patients and control with 25(OH)D deficiency (69.0 vs. 33.0), 25(OH)D insufficiency (25.0 vs. 42.0), and 25(OH)D sufficiency (6.0 vs. 25.0) (p < 0.001). MS was significantly associated with VDR polymorphisms among Apa1 and Fok1 genes. The genotype distribution for CC (47.0% vs. 53.0%; p = 0.002) and CA (37.0% vs. 45.0%; p = 0.001) genotypes among Apa1 VDR polymorphism, as well as among TT genotype (38.0% vs. 20.0%; p = 0.025) among Fok1 VDR gene polymorphism significantly differed between MS patients and healthy individuals. However, no associations were detected among Taq1 and Bsm1 VDR genotypes. VDR gene polymorphism of Apa1 and Fok1 variants may increase the risk of metabolic syndrome among Jordanian women.

Assessment of vitamin D status and vitamin D receptor polymorphism in Egyptian children with Type 1 diabetes

BackgroundThe endocrine system of vitamin D regulates about 3 % of the human genome. Vitamin D exerts its actions via a nuclear vitamin D receptor (VDR) which in turn regulates insulin secretion from the pancreas. VDR gene polymorphisms could have an impact on how autoimmune illnesses like Type 1 diabetes mellitus (T1DM) develop. We aimed to explore the relation between T1DM and VDR gene polymorphisms in Egyptian diabetic children and their siblings. MethodsEnzyme-linked immunosorbent assay was used to quantify 25(OH) vitamin D in the study, which had 179 participants (group 1 = 85 diabetic children, group 2 = 57 siblings of the patients, group 3 = 37 healthy controls). Real-time polymerase chain reaction (RT-PCR) was used to analyze the genotyping of the VDR gene polymorphisms Apa-I (rs7975232), Fok-I (rs2228570), Taq-I (rs731236) and Bsm-I (rs1544410). ResultsThe mean serum 25(OH) vitamin D levels was significantly lower in T1DM patients (14.99 ± 9.24 ng/mL) and siblings (16.31 ± 7.96 ng/mL) compared to the controls (19.48 ± 7.42 ng/mL) (p = 0.031). The genotypes distribution of VDR Fok-I (rs2228570) and Bsm-I (rs1544410) polymorphisms showed a significant difference between patients, siblings and controls as P = 0.001 and 0.026 respectively, while the VDR ApaI and TaqI polymorphisms did not. FokI-A allele frequency was significantly lower in T1DM patients and siblings than in controls (p < 0.001). FokI-AA genotype had a statistical significant higher vitamin D levels than other genotypes with p value of 0.024. ConclusionOur study found that T1DM children had lower vitamin D levels, and VDR FokI and BsmI gene polymorphisms were linked to T1DM in Egyptian children. Determining the relationship between vitamin D levels and VDR polymorphisms, particularly the FokI and other genetic analyses may aid in the early diagnosis of T1DM in children.

Role of VDR gene polymorphisms and vitamin D levels in normal and overweight patients with PCOS

Role of VDR gene polymorphisms and vitamin D levels in normal and overweight patients with PCOS

Serum 25-Hydroxyvitamin D, Vitamin D Receptor, and Vitamin-D-Binding Protein Gene Polymorphisms and Risk of Dementia Among Older Adults With Prediabetes.

The association between vitamin D and dementia risk in those with prediabetes remains uncertain. We aimed to evaluate the association of serum 25-hydroxyvitamin D (25OHD) with incident dementia among older adults with prediabetes, and examine whether apolipoprotein E (APOE) genotypes, vitamin D receptor (VDR), and vitamin-D-binding protein (VDBP) gene polymorphisms may modify this association. A total of 34237 participants aged ≥60 with prediabetes (HbA1c <6.5% and ≥5.7%) and without dementia at baseline were included from the UK Biobank. Serum 25-hydroxyvitamin D (25OHD) was measured using chemiluminescent immunoassay method. The primary outcome was incident all-cause dementia. Secondary outcomes included incident Alzheimer's disease (AD) and vascular dementia, respectively. The VDR and VDBP gene polymorphisms included single nucleotide polymorphisms of rs7975232, rs1544410, rs2228570, rs731236, and rs7041, rs4588, respectively. During a median follow-up of 11.8 years, 941 (2.7%) participants developed incident all-cause dementia. Overall, serum 25OHD was inversely associated with all-cause dementia (per standard deviation increment, adjusted hazard ratio: 0.82; 95% confidence interval: 0.75, 0.89). Similar trends were found for incident AD and vascular dementia. Furthermore, there was a stronger inverse relationship between serum 25OHD and all-cause dementia among VDR rs7975232 C allele noncarriers (p-interaction < 0.05). However, APOE Ɛ4, other VDR, and VDBP gene polymorphisms did not significantly modify the relation of serum 25OHD with incident all-cause dementia (all p-interactions >.05). There was an inverse association between serum 25OHD and incident dementia among older adults with prediabetes, especially in VDR rs7975232 AA allele carriers.

Contemporary perspectives on vitamin D provision in children and adolescents with obesity: a literature review and clinical case description

Introduction. Vitamin D deficiency is currently considered a global epidemic. Recent data highlight its pivotal role in the development of metabolic disorders, including obesity in children and adolescents. The aim of the study. To review current literature on the problem of vitamin D provision in children and adolescents with obesity, and to present a clinical case of a child with obesity, vitamin D deficiency, and accompanying metabolic disorders. Materials and methods: The study included literary review using content analysis, systemic and comparative analysis methods, as well as biblio-semantic methods to explore current data on the problem of vitamin D provision in children and adolescents with obesity. Sources included PubMed-NCBI, Medline, CochraneLibrary, EMBASE, ResearchGate databases using keywords as follows: children, adolescents, insulin resistance, obesity, vitamin D deficiency, VDR (Vitamin D Receptor) gene polymorphism, leptin, adipocytes. 66 English-language articles were analyzed, highlighting the role of vitamin D in human metabolic processes, its association with obesity, mechanisms of its deficiency impact including the inhibitory effect of leptin and interleukin 6, and the peculiarities of vitamin D biological action through nuclear VDR-mediated control of target genes. The prevalence of vitamin D deficiency in obese children in various countries was determined. Results. Obesity can induce altered protein binding and accelerated metabolic clearance of 25(OH)D, leading to reduced levels of 25(OH)D in the blood serum. It was identified that lower serum vitamin D levels and VDR gene polymorphism are associated with a predisposition to obesity in children and its severe consequences, this link apparently can help to identify VDR features that predict an increased risk of developing obesity, potentially leading to new therapeutic strategies for this metabolic condition. This will also increase public awareness about the psychosocial and clinical consequences of vitamin D deficiency and VDR gene polymorphism in obese children. Children with excessive weight and obesity are often diagnosed with hypovitaminosis, including vitamin D deficiency. Many studies around the world have found that vitamin D deficiency in obese children is at a critical stage and requires a change in diagnostic and treatment strategies. The clinical case described involves a patient who had obesity in association with vitamin D deficiency, and characteristic biochemical changes typical of this pathology. Biochemical indices included vitamin D deficiency, dyslipidemia, insulin resistance, leptin resistance, and hypothyroidism. Bioimpedance analysis revealed the presence of excessive body fat and its abnormal abdominal distribution in the child. Conclusions. Currently vitamin D deficiency is considered a global epidemic, causing concern among physicians and researchers of various specialties. Recent data underscore its leading role in the onset of metabolic disorders, including obesity in children and adolescents. The literature review confirmed the significant impact of vitamin D on the primary biochemical and metabolic processes in the human body, its crucial role in the emergence of obesity and various complications in children and adolescents. The presence of overweight or obesity in these patients requires a number of laboratory indeces, including serum vitamin D, leptin and thyroid hormones levels, protein, carbohydrate and lipid metabolism parameters, to be estimated. The use of bioimpedance analysis and ultrasound examination of the thyroid gland is advisable.

The Relationship between VDR Gene Polymorphisms Bsm1 and Apa1 with Breast Cancer Risk.

Background In addition to its multifaceted physiological functions, vitamin D is recognized for its protective role against cancer. To manifest its effects, vitamin D engages with the vitamin D receptor ( VDR ) gene responsible for its encoding. Investigations have unveiled that polymorphisms within the VDR gene exert influence over the expression and/or functionality of the VDR protein. Notably, certain VDR gene polymorphisms have emerged as particularly pertinent in the context of tumorigenesis, including Fok1 (rs2228570), Bsm1 (rs1544410), Taq1 (rs771236), and Apa1 (rs7975232). This study aims to scrutinize the correlation between the Bsm1 and Apa1 polymorphisms and the susceptibility to breast cancer development. Materials and Methods In this study, 50 patients suffering from breast cancer with less than 6 months breast cancer diagnosis and 50 healthy control individuals have been chosen. Restriction fragment length polymorphism polymerase chain reaction was used to determine the genotype of polymorphisms. Results The results of the statistical analysis showed that among the studied polymorphisms, there was no correlation with the development of breast cancer. Conclusion Studies on various cancers have produced inconsistent results regarding vitamin D's role in the development and progression of cancer. Therefore, further research is necessary to determine vitamin D's role in cancer development and progression.

Влияние экзогенных и генетических факторов на уровень витамина D у детей с бронхиальной астмой в трех регионах Российской Федерации

The high prevalence and socioeconomic burden of bronchial asthma (BA) encourage scientists to continue active study of both exogenous and genetic factors influencing the course of BA. The connection between vitamin D deficiency and asthma in children has been shown in many studies. Work on the analysis of vitamin D content in patients with asthma is often carried out without taking into account the geographical location and level of insolation, and is also often performed on small samples of patients, which makes it difficult to interpret the results obtained. Studies devoted to the connection between genetic polymorphisms of the VDR gene and AD with a comprehensive analysis of the influence of exogenous and endogenous factors are rare and provide contradictory results. That is why the present study compared the supply of vitamin D with clinical phenotypes of asthma, the response to cholecalciferol supplementation and genetic markers that influence 25(OH)D metabolism among children of three equidistant regions of the Russian Federation. Objective. Тo study the 25(OH)D content of children with bronchial asthma (BA) depending on exogenous factors (region of residence, volume of basic therapy, intake of vitamin D from food, dietary supplementation with cholecalciferol) and endogenous factors (gender, age, course characteristics AD, VDR gene polymorphism genotypes). Patients and methods. The study included 160 children with asthma (median age 8.55 years), the comparison group consisted of 333 children (median age 6.4 years). All subjects were assessed for calcidiol levels in different seasons of the year. Testing of polymorphic variants of the VDR gene (c.1206T&gt;C, c.1175-9G&gt;T, c.152T&gt;C, c.1174+283G&gt;A) was carried out using PCR and RFLP analysis. Results. The average level of 25(OH)D in patients with BA and healthy children was significantly different and was 21.3 ng/ml in patients with BA and 29.6 ng/ml in healthy children (p &lt; 0.01). It was revealed that 89.62% of patients with asthma and 60.8% of healthy children had a low supply of vitamin D (p &lt; 0.05). The frequency of severe deficiency in children with asthma was 23.7%; no pronounced deficiency was recorded among healthy children. A 25(OH)D concentration of 10–20 ng/ml was more often observed in asthma (46.66%) compared to healthy children (26.5%). It was found that 25(OH)D deficiency 21–29 ng/ml was more often recorded in healthy children (34.3%) compared to BA (19.25%, p &lt; 0.05). Low 25(OH)D levels are observed among 92.6% of patients with BA from Krasnoyarsk, among all patients with BA from Stavropol and 70.6% of patients with BA from Moscow. There was no effect of vitamin D content in food on the concentration of 25(OH)D in the blood. Taking vitamin D in doses from 500 IU to 1500 IU per day does not significantly increase the level of 25(OH)D and achieve optimal vitamin D status. Patients with the minor genotype AA of the BsmlI VDR gene polymorphism do not respond by increasing the level of 25(OH)D in response for supplementation. Conclusion. The status of vitamin D in asthma in the Russian Federation does not depend on the climatic and geographical characteristics of the region of residence, the intake of vitamin D from food and PSS during prophylaxis with standard doses of cholecalciferol, but is determined by gender, age, season of the year, lack of intake or intake of a low preventive dose cholecalciferol (less than 1000 IU), as well as the influence of BsmlI polymorphism of the VDR gene. Key words: bronchial asthma, children, vitamin D, supplementation, VDR gene

Frequency of Healthy Control Genotype of VDR Gene Polymorphisms in the Saudi Population of the Ha'il Region: A Comparative Study with Worldwide Population.

Genetic polymorphisms in the vitamin D receptor (VDR) may influence the biological effects of vitamin D and increase a person's susceptibility to cancer. Previous studies have shown that different ethnic groups exhibit varying frequencies of the VDR gene variants TaqI, ApaI, FokI, and BsmI. However, the allelic distribution of these VDR polymorphisms in the Saudi population of Ha'il region is not sufficiently explored. In this study, efforts were made to ascertain the frequency of VDR polymorphisms in the Saudi population of Ha'il region, and then comparison was made for VDR polymorphism rates with other populations of the world. Allele and genotype frequencies of VDR TaqI, ApaI, BsmI and FokI gene was determined. The frequency distribution for the variant allele of VDR TaqI, ApaI, BsmI and FokI was found to be 70, 33, 50 and 25%, respectively. A significant frequency distribution was found for VDR-TaqI, ApaI and FokI variants in comparison with other populations of the world. Whereas, almost all of the studies dealing with VDR-FokI failed to show substantial difference while comparing with the data reported from the population of Ha'il region of Saudi Arabia. A significant pattern in the frequency of VDR gene variations have been found in the Saudi population of Ha'il region, which may be attributed to ethnic variance. The understanding of the worldwide distribution of VDR markers could help with high-risk screening of those who are exposed to environmental hazards and people of Ha'il region, who are predispose to cancer.

VDR gene TaqI (rs731236) polymorphism affects gut microbiota diversity and composition in a Caucasian population.

The VDR gene is identified as a crucial host factor, influencing the gut microbiota. The current research focuses on an observational study that compares gut microbiota composition among individuals with different VDR gene TaqI polymorphisms in a Caucasian Spanish population. This study aims to elucidate the interplay between genetic variations in the VDR gene and the gut microbial composition. 87 healthy participants (57 men, 30 women), aged 18 to 48 years, were examined. Anthropometric measures, body composition, and dietary habits were assessed. VDR gene polymorphism TaqI rs731236 was determined using TaqMan assays. The V3 and V4 regions of the 16S rRNA gene were sequenced to study bacterial composition, which was analyzed using QIIME2, DADA2 plugin, and PICRUSt2. Statistical analyses included tests for normal distribution, alpha/beta diversity, ADONIS, LEfSe, and DESeq2, with established significance thresholds. No significant differences in body composition or dietary habits were observed based on VDR genotypes. Dietary intake analysis revealed no variations in energy, macronutrients, or fiber among the different VDR genotypes. Fecal microbiota analysis indicated significant differences in alpha diversity as measured by Faith's Phylogenetic Diversity index. Differential abundance analysis identified taxonomic disparities, notably in the genera Parabacteroides and Butyricimonas. Overall, this study suggests potential associations between genetic variations in the VDR gene and the composition and function of gut microbiota.

Vitamin D Receptor Gene Polymorphisms and Association with Vitiligo in Indonesian Population.

Vitiligo is an acquired depigmenting skin disorder due to the loss of melanocyte function in the epidermis and hair follicles. The pathogenesis of vitiligo is multifactorial, with genetics being a predisposing factor. Previous studies had varying results regarding whether or not polymorphisms of vitamin D receptor (VDR) gene are associated with the risk of vitiligo in specific populations. This study investigated the association between three frequently analyzed VDR gene polymorphisms (ApaI, BsmI, TaqI) and susceptibility to vitiligo in Indonesian population. Thirty-four vitiligo patients and 34 age- and sex-matched healthy subjects aged ≥18 years old were recruited in the Dermatology and Venereology Outpatient Clinic of Dr. Hasan Sadikin General Hospital, Bandung, Indonesia. Genomic deoxyribonucleic acid (DNA) was extracted from the peripheral blood using a DNA isolation kit. VDR gene polymorphisms (ApaI, BsmI, and TaqI) were investigated using the polymerase chain reaction-restriction-fragment length polymorphism method. The differences of genotype distributions and allele frequencies were statistically compared between case and control groups using Chi-square test. VDR gene polymorphisms were identified in 68 participants, consisting of Aa (n = 14), aa (n = 20), Bb (n = 15), bb (n = 19), and TT (n = 34) genotypes in the case group. In the control group, Aa (n = 6), aa (n = 28), Bb (n = 17), bb (n = 17), and TT (n = 34) genotypes were identified. However, only subjects with ApaI Aa genotype polymorphism had a 3.267-fold increased risk of developing vitiligo. This study showed that ApaI Aa genotype polymorphism of the VDR gene increases the risk of vitiligo in Indonesian population.

Assessment of Cdx2 polymorphism in Iranian women with polycystic ovary syndrome

BackgroundWomen’s fertility is affected by polycystic ovarian syndrome (PCOS) as an endocrine disorder with characteristic symptoms such as insulin resistance, polycystic ovaries, menstrual irregularities, and obesity. In polycystic ovarian syndrome, the vitamin D endocrine system is regulated by the vitamin D receptor (VDR) associated with type II diabetes, endocrine dysfunctions, and insulin resistance. Therefore, the current paper deals with the investigation of the connection between Cdx2 VDR gene polymorphism and the biochemical factors in obese PCOS women.Material and methodsIn the current case–control study, 40 obese women without PCOS and 38 obese women with PCOS were enrolled in May–September 2016. Insulin, IGF1, FBS, and HOMA-IR were examined for the participants along with the allelic and genotypic frequency of Cdx2 polymorphism G/A (rs11568820) from Isfahan Fertility and Infertility Center, Iran. The ASM-PCR (multiplex allele-specific PCR) technique was utilized in this regard.ResultsThe age of PCOS women was less (P < 0.001) than the controls. In PCOS women, insulin, FBS, and HOMA-IR serum levels were higher than in the control women (all P values 0.05). For GG, AG, AA,A, and G Cdx2(A/G) genotypic/allelic frequencies were 84.2%, 15.8%, 0%, 7.9%, and 92.1% in cases and 87.5%, 12.5%, 0%, 6.3%, and 93.8% in controls, respectively. HOMA-IR (P = 0.047 and P = 0.033, respectively) and insulin than those with the AG genotype were in PCOS women with the GG Cdx2 genotype. The highest IGF-1 mean value (P = 0.020) was found for the AG genotype in PCOS. In our study, a significant relation was found only between PCOS and FBS, in terms of a logistic regression analysis of Cdx2 and parameters.ConclusionIn the present study, it was indicated that the GG genotype in PCOS subjects was associated with the IGF-1, HOMA-IR, and insulin. Similarly, no association was found between obese PCOS patients and Cdx2 in the 1a promoter area of the VDR gene in our study.

Association between vitamin D receptor gene polymorphism and cardiomyopathy in response to adriamycin treatment among breast cancer patients

Abstract Background Chemotherapy-induced cardiomyopathy (CIC) is a common side effect affecting patients with breast cancer treated with anthracyclines chemotherapeutic agents. Vitamin D receptor gene polymorphism seemed to play a crucial role in developing CIC, as vitamin D deficiency was found to increase the risk of many diseases including colon, breast, prostate and ovarian cancer. Purpose The current study is primarily to investigate the effect of vitamin D receptor gene polymorphism (ApaI, TaqI, BsmI and FokI) on the incidence of CIC in adult patients with local/advanced or metastatic breast cancer on anthracyclines. Another aim is to detect the association of the gene polymorphism with the response to treatment with chemotherapeutic agents. Moreover, the current study investigated the expression of miR-155 in patients and analyzed its relationship with CIC occurrence. Methods This case-control study recruited 60 breast cancer patients with CIC and 30 breast cancer patients without CIC from cardiology and oncology clinics between February 2017 and November 2021. Genomic DNA was extracted from peripheral blood samples and VDR gene polymorphisms were detected using TaqMan techniques. Results For the ApaI (rs7975232) and TaqI (rs731236) single-nucleotide polymorphisms (SNPs), the heterozygous (CA) and heterozygous (GA) genotypes increased the risk of CIC among breast cancer patients compared to the control group (OR = 4.31, P &amp;lt; 0.001; OR = 3.2, P = 0.015, respectively). In contrast, homozygous (CC) carriers of the BsmI SNP (rs1544410) had a significantly lower risk for CIC among breast cancer patients (P &amp;lt; 0.001). Finally, for the FokI SNP (rs2228570), there was no significant association with CIC risk. Levels of miR-155 were significantly increased in CIC group compared to the control group (P = 0.015). Conclusion The C allele carriers of ApaI SNP and A allele carriers of TaqI SNP are at higher risk of CIC among breast cancer patients; in contrast, the homozygous (CC) carriers of the BsmI SNP are protective against CIC among breast cancer patients. Additionally, higher levels of miR-155 are associated with CIC increased risk among breast cancer patients.

Effect of vitamin D receptor genetic polymorphism on the clinical response to angiotensin converting enzyme inhibitors therapy among breast cancer patients with chemotherapy induced cardiomyopathy

Abstract Background Blockade of the renin-angiotensin-aldosterone system (RAAS) is the cornerstone treatment of chemotherapy induced cardiomyopathy (CIC) yet, variability in response to angiotensin converting enzyme inhibitors (ACEIs) acting on the RAAS is well-documented. Vitamin D was found to play a role in regulating RAAS. Previous studies revealed an inverse relationship between levels of vitamin D in serum and RAAS activation. Purpose The current study is primarily to evaluate the association between genetic variants in the vitamin D receptor (VDR) and clinical response to ACEIs among breast cancer patients receiving chemotherapy with CIC. Methods A total of 60 breast cancer patients with CIC (mean ejection fraction 30%) on β-blocker therapy were started on a ACEIs and followed for 6 months. Post-ACEIs-treatment changes in ejection fraction (EF) and serum potassium (K) were evaluated. We genotyped VDR gene polymorphisms including; ApaI (rs7975232), TaqI (rs731236), BsmI (rs1544410) and FokI (rs2228570) variants using TaqMan technique. Stepwise linear regression was performed to identify genetic and clinical factors associated with variability in ACEIs response, with adjustment for all potential confounding covariates. Results BsmI (rs1544410) (CT) heterozygous and TaqI (rs731236) (GA) genotypes had a significant increase in EF (12.8% and 10.8 %, respectively) and serum K (1.1 mEq/L and 0.91 mEq/L respectively); adjusted-p = 0.0001 and 0.004 for ∆EF and adjusted-p = 0.005 and 0.002 for ∆K. In contrast, (AA) homozygous carriers of the ApaI SNP (rs7975232) had a smaller increase in EF (∆EF = 1.2%) and K (∆K = 0.1 mEq/L) compared to (CA) (∆EF = 6.5%, ∆K = 0.73mEq/L) and (CC) (∆EF = 9%, ∆K = 0.9mEq/L) carriers; adjusted-p = 0.003 for ∆EF, adjusted-p = 0.004 for ∆K. Finally, for the FokI SNP (rs2228570), there was no significant change in EF and serum K level. Conclusion The results from this study highlight that BsmI (rs1544410) and TaqI (rs731236) are strong predictors of response to ACEIs therapy in chemotherapy-induced cardiomyopathy (CIC).

Association between VDR genetic polymorphisms and risk of gestational diabetes mellitus in the Chinese population.

Abnormal metabolism of vitamin D was the primary mechanism in many pregnancy diseases. Our study was the first to examine the hypothesis that VDR gene polymorphisms contribute to the risk of gestational diabetes mellitus (GDM) in the Chinese population at high altitudes. One hundred and eighteen women with GDM and 104 women with normal glucose tolerance (NGT) were included in this study using a case-control design. Four single nucleotide polymorphisms (g.47879112G>A, g.47846052C>T, g.47844974A>G, and g.47845054C>A) of mother and fetus were genotyped. Maternal and fetal frequency of the A allele of g.47879112G>A was significantly increased in women with GDM than in those with NGT (p<.05). A correlation between the AA homozygous genotype of g.47879112G>A and GDM was noted. Compared with non-carriers, A allele carriers showed higher fasting plasma insulin and two-hour post-challenge plasma glucose (2h-PPG), and lower levels of vitamin D. Furthermore, both maternal and fetal 4-marker haplotype ACCG were found to be significantly associated with GDM (p<.05). Association and haplotype analysis indicated that the A allele of g.47879112G>A could be a risk factor for GDM development in the Chinese population at high altitudes. Additionally, the VDR gene polymorphism of the fetus and mother may have a synergistic effect. The VDR polymorphism is associated with an increased risk of GDM and may be useful for predicting the development of the disease.

Association analysis between the VDR gene variants and type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is recognized as a complex metabolic which has affected the lives of millions of people around the world. Vitamin D receptor (VDR) gene polymorphisms have been suggested to be a vital contributor to the development of T2DM. However, the association between VDR gene polymorphisms and T2DM remains controversial.We have investigated the association between two VDR gene polymorphisms (rs731236 and rs1544410) and T2DM in an Iranian population. A total of 148 T2DM patients and 100 normal controls were recruited in this study. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to perform genotyping. The results of the present research revealed that the frequency of the rs731236 C allele was significantly higher in T2DM patients than in normal controls (p = 0.044). The CC genotype of rs731236 was connected with an increased risk of T2DM (OR = 2.85, 95% CI = 1.06-7.69, p = 0.039). However, no significant difference in the frequency of the rs1544410 C allele between T2DM patients and normal controls was observed (p = 0.918). Our findings were suggestive of the rs731236 polymorphism of the VDR as a risk factor for developing T2DM in the Iranian population, while rs1544410 polymorphism may not be associated with T2DM susceptibility. Further research is needed to approve these findings in other populations and to clarify the underlying mechanisms involved in such an association. The online version contains supplementary material available at 10.1007/s40200-023-01323-0.