The Role of Polymorphisms in Vitamin D-Related Genes in Response to Vitamin D Supplementation

Background. Vitamin D deficiency represents a major healthcare problem. Vitamin D status is influenced by genetic and environmental determinants. Several observational studies have evaluated the association of single-nucleotide polymorphisms (SNPs) in vitamin D-related genes and vitamin D levels. Nevertheless, little is known about the role of these SNPs in the response to vitamin D supplementation. We conducted an interventional study to define the association between SNPs in vitamin D-related genes and the response to vitamin D supplementation in 100 self-reported healthy women of Arab ancestry for the majority. Methods. A total of 100 healthy female subjects received a weekly oral dose of 50,000 IU vitamin D for 12 weeks. Serum vitamin D concentration and metabolic profiles were measured at baseline and 12 weeks post-vitamin D supplementation. The genotypes of 37 SNPs selected from previously reported vitamin D-related genes have been assessed by Fluidigm genotyping assay. Results. Rs731236 (VDR gene) and rs7116978 (CYP2R1 gene) showed a significant association with vitamin D status. The rs731236 GG genotype and the rs7116978 CC genotype were associated with a “vitamin D sufficiency” state. Rs731236 GG and rs7116978 CC genotypes showed a higher response to vitamin D supplementation. Transcription factor binding site prediction analysis showed altered binding sites for transcription factors according to the different rs7116978 alleles. Interestingly, the 37 SNPs previously established to play a role in vitamin D-related pathways explained very little of the response to vitamin D supplementation in our cohort, suggesting the existence of alternative loci whose number and effect size need to be investigated in future studies. Conclusion. In this paper, we present novel data on vitamin D-related SNPs and response to vitamin D supplementation demonstrating the feasibility of applying functional genomic approaches in interventional studies to assess individual-level responses to vitamin D supplementation.

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Vitamin D Status Impacts Genital Mucosal Immunity and Markers of HIV-1 Susceptibility in Women

Nutrients ◽

10.3390/nu12103176 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3176

Author(s):

Sharon M. Anderson ◽

Andrea R. Thurman ◽

Neelima Chandra ◽

Suzanne S. Jackson ◽

Susana Asin ◽

...

Keyword(s):

Vitamin D ◽

Reproductive Tract ◽

Serum Vitamin ◽

Female Reproductive Tract ◽

High Dose ◽

Vitamin D Status ◽

Serum Vitamin D ◽

Vitamin D Levels ◽

Hiv 1

While vitamin D insufficiency is known to impact a multitude of health outcomes, including HIV-1, little is known about the role of vitamin D-mediated immune regulation in the female reproductive tract (FRT). We performed a pilot clinical study of 20 women with circulating 25(OH)D levels <62.5 nmol/L. Participants were randomized into either weekly or daily high-dose oral vitamin D supplementation groups. In addition to serum vitamin D levels, genital mucosal endpoints, including soluble mediators, immune cell populations, gene expression, and ex vivo HIV-1 infection, were assessed. While systemic vitamin D levels showed a significant increase following supplementation, these changes translated into modest effects on the cervicovaginal factors studied. Paradoxically, post-supplementation vitamin D levels were decreased in cervicovaginal fluids. Given the strong correlation between vitamin D status and HIV-1 infection and the widespread nature of vitamin D deficiency, further understanding of the role of vitamin D immunoregulation in the female reproductive tract is important.

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OBSERVATIONAL STUDY OF PREGNANCY VITAMIN D STATUS AND RISK OF PREECLAMPSIA

10.36106/ijsr/9525819 ◽

2021 ◽

pp. 1-3

Author(s):

Manaswita Samanta ◽

Shweta Pathak ◽

Debarshi Jana

Keyword(s):

Vitamin D ◽

Early Pregnancy ◽

Serum Vitamin ◽

Vitamin D Supplementation ◽

Vitamin D Status ◽

Hydroxyvitamin D ◽

Serum Vitamin D ◽

Vitamin D Levels ◽

25 Hydroxyvitamin D ◽

Risk Of Preeclampsia

Introduction:Low vitamin D status, among other risk factors, is linked to the development of preeclampsia. Systematic reviews and metaanalyses have concluded that low serum vitamin D levels (25-hydroxyvitamin D [25OHD]) in pregnancy are associated with a higher risk of preeclampsia and suggest a preventive role of vitamin D supplementation. Aim:To examine the association between maternal serum 25-hydroxyvitamin D (25[OH]D) concentration in early pregnancy and the subsequent diagnosis of preeclampsia. Material and methods:This prospective case control study was carried out at Department of Obstetrics and Gynecology, College of medicine and JNM Hospital, Kalyani, Nadia. Duration of the study was one and half year study period from March 2018-August 2019. Total 100 cases attending regular antenatal OPD was included provided they full the inclusion criteria. Result:It was found that in preeclampsia, 4(66.7%) patients had Vitamin-D Deciency and 2(33.3%) patients had Insufciency Vitamin-D. Association of Vitamin-D vs. preeclampsia was not statistically signicant (p=0.3135). It was found that in preeclampsia, 6(100.0%) patients had no Previous Eclampsia. Association of Previous Eclampsia vs. preeclampsia was not statistically signicant (p=0.6991965055). Conclusion:We concluded that maternal vitamin D deciency may be an independent risk factor for preeclampsia. Vitamin D supplementation in early pregnancy should be explored for preventing preeclampsia.

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Maternal early pregnancy vitamin D status in relation to fetal and neonatal growth: results of the multi-ethnic Amsterdam Born Children and their Development cohort

British Journal Of Nutrition ◽

10.1017/s000711451000022x ◽

2010 ◽

Vol 104 (1) ◽

pp. 108-117 ◽

Cited By ~ 181

Author(s):

Evelien R. Leffelaar ◽

Tanja G. M. Vrijkotte ◽

Manon van Eijsden

Keyword(s):

Vitamin D ◽

Birth Weight ◽

Early Pregnancy ◽

Serum Vitamin ◽

Ethnic Disparities ◽

Vitamin D Supplementation ◽

Vitamin D Status ◽

Serum Vitamin D ◽

Vitamin D Levels ◽

Neonatal Growth

Low vitamin D levels during pregnancy may account for reduced fetal growth and for altered neonatal development. The present study explored the association between maternal vitamin D status measured early in pregnancy and birth weight, prevalence of small-for-gestational-age (SGA) infants and postnatal growth (weight and length), as well as the potential role of vitamin D status in explaining ethnic disparities in these outcomes. Data were derived from a large multi-ethnic cohort in The Netherlands (Amsterdam Born Children and their Development (ABCD) cohort), and included 3730 women with live-born singleton term deliveries. Maternal serum vitamin D was measured during early pregnancy (median 13 weeks, interquartile range: 12–14), and was labelled ‘deficient’ ( ≤ 29·9 nmol/l), ‘insufficient’ (30–49·9 nmol/l) or ‘adequate’ ( ≥ 50 nmol/l). Six ethnic groups were distinguished: Dutch, Surinamese, Turkish, Moroccan, other non-Western and other Western. Associations with neonatal outcomes were analysed using multivariate regression analyses. Results showed that compared with women with adequate vitamin D levels, women with deficient vitamin D levels had infants with lower birth weights ( − 114·4 g, 95 % CI − 151·2, − 77·6) and a higher risk of SGA (OR 2·4, 95 % CI 1·9, 3·2). Neonates born to mothers with a deficient vitamin D status showed accelerated growth in weight and length during the first year of life. Although a deficient vitamin D status influenced birth weight, SGA risk and neonatal growth, it played a limited role in explaining ethnic differences. Although vitamin D supplementation might be beneficial to those at risk of a deficient vitamin D status, more research is needed before a nationwide policy on the subject can be justified.

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Role of Vitamin D in Systemic Sclerosis: A Systematic Literature Review

Journal of Immunology Research ◽

10.1155/2021/9782994 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Alexandra-Diana Diaconu ◽

Iustina Ostafie ◽

Alexandr Ceasovschih ◽

Victorița Șorodoc ◽

Cătălina Lionte ◽

...

Keyword(s):

Vitamin D ◽

Systemic Sclerosis ◽

Serum Vitamin ◽

Final Analysis ◽

Vitamin D Supplementation ◽

Bone Homeostasis ◽

Traditional Role ◽

Serum Vitamin D ◽

Vitamin D Levels

Background. Systemic sclerosis (SSc) is a chronic multisystem autoimmune condition defined by a complex pathobiology, comprising excessive fibrosis of skin and internal organs, peripheral vasculopathy with endothelial cell dysfunction, inadequate vascular repair and neovascularization, and aberrant immunity. Vitamin D is a steroid hormone with pleiotropic effects beyond its traditional role in calcium and bone homeostasis. Since vitamin D has immunomodulatory, cardioprotective, and antifibrotic properties, it could potentially interfere with SSc pathogenesis. Suboptimal vitamin D levels are classically recognized in scleroderma, irrespective of clinical and serological phenotype. Aim. This systematic review is aimed at investigating and clarifying the role of vitamin D in SSc and emphasizing the association of vitamin D status with different clinical settings. Methods and Results. A systematic online search was performed, using PubMed databases to collect articles on the topic of vitamin D in SSc. The final analysis included 40 eligible articles. Conclusions. Hypovitaminosis D is common in SSc patients and could be associated with clinical and serologic patterns of the disease. Intervention for low serum vitamin D levels in SSc pathogenesis remains controversial, as well as the significance of vitamin D supplementation in such patients.

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Using genetic variants to evaluate the causal effect of serum vitamin D concentration on COVID-19 susceptibility, severity and hospitalization traits: a Mendelian randomization study

Journal of Translational Medicine ◽

10.1186/s12967-021-02973-5 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Zhiyong Cui ◽

Yun Tian

Keyword(s):

Vitamin D ◽

Fixed Effects ◽

Mendelian Randomization ◽

Causal Effect ◽

Serum Vitamin ◽

Vitamin D Supplementation ◽

Sensitivity Analyses ◽

Global Test ◽

Serum Vitamin D

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic has struck globally and is exerting a devastating toll on humans. The pandemic has led to calls for widespread vitamin D supplementation in public. However, evidence supporting the role of vitamin D in the COVID-19 pandemic remains controversial. Methods We performed a two-sample Mendelian randomization (MR) analysis to analyze the causal effect of the 25-hydroxyvitamin D [25(OH)D] concentration on COVID-19 susceptibility, severity and hospitalization traits by using summary-level GWAS data. The causal associations were estimated with inverse variance weighted (IVW) with fixed effects (IVW-fixed) and random effects (IVW-random), MR-Egger, weighted edian and MR Robust Adjusted Profile Score (MR.RAPS) methods. We further applied the MR Steiger filtering method, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test and PhenoScanner tool to check and remove single nucleotide polymorphisms (SNPs) that were horizontally pleiotropic. Results We found no evidence to support the causal associations between the serum 25(OH)D concentration and the risk of COVID-19 susceptibility [IVW-fixed: odds ratio (OR) = 0.9049, 95% confidence interval (CI) 0.8197–0.9988, p = 0.0473], severity (IVW-fixed: OR = 1.0298, 95% CI 0.7699–1.3775, p = 0.8432) and hospitalized traits (IVW-fixed: OR = 1.0713, 95% CI 0.8819–1.3013, p = 0.4878) using outlier removed sets at a Bonferroni-corrected p threshold of 0.0167. Sensitivity analyses did not reveal any sign of horizontal pleiotropy. Conclusions Our MR analysis provided precise evidence that genetically lowered serum 25(OH)D concentrations were not causally associated with COVID-19 susceptibility, severity or hospitalized traits. Our study did not provide evidence assessing the role of vitamin D supplementation during the COVID-19 pandemic. High-quality randomized controlled trials are necessary to explore and define the role of vitamin D supplementation in the prevention and treatment of COVID-19.

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Influence of serum vitamin D status on severe sarcopenia among female patients with rheumatoid arthritis: the KURAMA database

10.21203/rs.3.rs-697981/v1 ◽

2021 ◽

Author(s):

Hiroto Minamino ◽

Masao Katsushima ◽

Mie Torii ◽

Wataru Yamamoto ◽

Yoshihito Fujita ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Vitamin D ◽

Muscle Mass ◽

Gait Speed ◽

Serum Vitamin ◽

Vitamin D Status ◽

Serum Vitamin D ◽

Increased Risk ◽

Vitamin D Levels ◽

High Prevalence

Abstract Sarcopenia is an age-related disease with an increased risk of mortality. It is emerging that low serum vitamin D (25(OH)D) affects the sarcopenic state in general, but in rheumatoid arthritis (RA), these associations are not understood although the prevalence of vitamin D insufficiency is high in RA. We conducted a cross-sectional study of older female outpatients from our cohort (KURAMA) database. We measured skeletal muscle mass, handgrip strength, and gait-speed to diagnose severe sarcopenia. The serum 25(OH)D concentration was measured using electrochemiluminescence immunoassay. A total of 156 Patients (sarcopenia:44.9%, severe sarcopenia: 29.5%, and without sarcopenia: 25.6%) were enrolled. Classification of vitamin D status at a cutoff point of median 25(OH)D concentration revealed that low 25(OH)D status was associated with a high prevalence of severe sarcopenia and with low measured values of muscle mass, handgrip, and gait-speed. Furthermore, multiple regression analysis identified that low 25(OH)D status was associated with a high prevalence of severe sarcopenia (OR 6.00; 95% CI 1.99–18.08). In components of sarcopenia, both low physical performance and muscle mass were associated with low 25(OH) status. In conclusion, vitamin D levels are associated with severe sarcopenia and its components, and modification of vitamin D status including vitamin D supplementation may play a role in improving sarcopenia in RA.

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P–662 Study on D-vitamin, AMH and insulin interrelation in Polycystic Ovary Syndrome (PCOS) patients

Human Reproduction ◽

10.1093/humrep/deab130.661 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

A Coc. Lizarraga ◽

S Lindenberg ◽

G Juu. Almind ◽

F Lindenberg

Keyword(s):

Insulin Resistance ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Serum Vitamin ◽

Serum Vitamin D ◽

Vitamin D Levels ◽

Group A ◽

D Values ◽

Group B

Abstract Study question Is vitamin D deficiency more prevalent in PCOS patients? Is there a link between vitamin D levels and metabolic status in PCOS subjects? Summary answer An inverse relationship between vitamin D levels and metabolic status was demonstrated and it is thought to be responsible of its pathogenesis. What is known already PCOS is a multifactorial condition, characterised by failure in oogenesis and anovulation. Obesity is a common condition linked to its clinical features and studies have reported inverse associations between BMI and severity of the condition. Furthermore, 67–85% of PCOS patients have vitamin D deficiency. Low levels of vitamin D have been found to be closely related to insulin resistance, obesity, or hyperandrogenism and there is a significant association between serum vitamin D levels and reproductive function. Other factors such as AMH have also been described as possibly involved in the pathophysiology. Study design, size, duration We performed a retrospective, analytical and observational study in the Copenhagen Fertility Center. Patients referred with cycle abnormalities, hirsutism, and infertility were evaluated. A total of 778 women were enrolled consecutively from January 2019 to October 2020. Subjects who had major medical disorders were excluded. We selected those in which vitamin D was measured in the baseline analysis selecting a total of 396 patients. The further analysis has been carried out from 100 randomly selected patients. Participants/materials, setting, methods Blood samples were drawn after overnight fasting. They were all assayed in the same laboratory. Biochemical parameters were analyzed using descriptive statistics. Same parameters were studied after dividing into vitamin D deficiency group or optimal levels using a multiple t-test. Correlation between variables was determined. Graphpad Prism program version 8 was used to perform the calculations. The level of statistical significance was set at P-value < 0.05. Main results and the role of chance A total of 100 subjects fulfilling the inclusion criteria were selected randomly from 396 PCOS women. Serum vitamin D concentrations were highly variable ranging from 16 nmol/L to 175 nmol/L. The prevalence of vitamin D deficiency was 24% and 41% of the subjects were classified as vitamin D insufficient. Only 35% of our patients had optimal vitamin D values. We compared data between the group with optimal values of vitamin D (Group A) versus the group with insufficient/deficient vitamin D values (Group B). We found statistical difference between groups in PTH values, being notably higher in group B compared with group A. Despite no statistically significant difference was obtained, it is important to highlight that the mean of SHBG was lower in group B and the mean of androstenedione, AMH, FAI and HOMA-IR were much higher in this group as well. Following the HOMA-IR criteria, 55% of patients had insulin resistance. Specifically, 26% had moderate insulin resistance and 29% severe insulin resistance. Levels of vitamin D were negatively correlated with FAI, AMH and HOMA-IR and positively correlated with HDL-Cholesterol and SHBG. Statistically significant differences were evidenced in the correlation between vitamin D and FAI and SHBG. Limitations, reasons for caution This is a retrospective observational study on a consecutive admitted patient group with a lack of a control group. Another limitation is the small sample size. It is difficult to generalize with other degrees of severity. We didn’t assess seasonal variability or if they were taking any vitamin D supplementation. Wider implications of the findings: Properly randomized clinical trials are mandatory to achieve more conclusive results about the role of vitamin D. Available evidence is promising but not sufficient to draw final conclusions. The aim is to better understand the pathophysiology of the condition and the factors involved and to find new target treatments. Trial registration number 1

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Association Between cardiometabolic risk factor and responsiveness to vitamin D supplementation: A New Approach using Artificial Neural Network analysis

10.21203/rs.3.rs-76964/v1 ◽

2020 ◽

Author(s):

Elahe Allahyari ◽

Parichehr Hanachi ◽

Seyed Jamal Mirmoosavi ◽

Gordon A. Ferns ◽

Afsane Bahrami ◽

...

Keyword(s):

Vitamin D ◽

Risk Factor ◽

Cardiometabolic Risk ◽

Serum Vitamin ◽

Vitamin D Supplementation ◽

Cardiometabolic Risk Factor ◽

Baseline Serum ◽

Serum Vitamin D ◽

Vitamin D Levels ◽

Artificial Neural

Abstract BackgroundAccumulating data have highlighted the prominence of supplementation as an effective approach for vitamin D deficiency. But individuals vary in their response to vitamin D supplementation. In this study, the effect of cardiometabolic risk factors were evaluate on magnitude of response to vitamin D supplementation by using novel statistical analysis, artificial neural networks(ANNs).Methods608 participants aged between 12 to 19 years old were assed in this prospective interventional study. Nine vitamin D capsules containing 50000IU vitamin D/weekly were given to all participants over the 9 week period. The change in serum 25(OH)D level was calculated as the difference between post-supplementation and basal levels. Suitable ANNs model were selected between different algorithms in the hidden and output layers and different numbers of neurons in the hidden layer. Then, the major determinants in predicting response to vitamin D supplementations were identified (Trial registration: IRCT201509047117N7; 2015-11-25; Retrospectively registered)ResultsSigmoid in both hidden and output layers with 4 hidden neurons had acceptable sensitivity, specificity and accuracy area under the ROC curve in our study. Baseline serum vitamin D (30.4%), waist to hip ratio (10.5%), BMI (10.5%), systolic blood pressure (8%), heart rate (6.4%), and waist circumference (6.1%) were the greatest importance in predicting the response in serum vitamin D levels. ConclusionWe provide the first attempt to relate anthropometric specific recommendations to attain serum vitamin D targets. With the exception of cardiometabolic risk factor, the relative importance of other factors and the mechanisms by which these factors may affect the response requires further analysis in future studies.

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Low Serum Vitamin D is Independently Associated with Acute Ischemic Stroke

Medicine Today ◽

10.3329/medtoday.v30i1.35564 ◽

2018 ◽

Vol 30 (1) ◽

pp. 34-37

Author(s):

Md Mahabubul Islam Majumder ◽

Md Nazmul Hasan Chowdhury ◽

Ashiqur Rahman Khan ◽

Tarek Ahmed ◽

Saleh Ahmed

Keyword(s):

Vitamin D ◽

Ischemic Stroke ◽

Acute Stroke ◽

Acute Ischemic Stroke ◽

Serum Vitamin ◽

Multivariate Logistic Regression Analysis ◽

Vitamin D Status ◽

Serum Vitamin D ◽

Vitamin D Levels ◽

Low Serum

Low serum vitamin D levels have been associated with various vascular diseases. Very little is known its association with acute stroke in Bangladeshi population. We therefore sought to assess whether low serum 25- hydroxyvitamin D, a marker of vitamin D status is associated with acute stroke. We performed a prospective study in Comilla Medical Collage, Comilla, from November 2016 to November 2017. All the patients diagnosed as acute ischemic stroke on the basis of CT scan or MRI of brain. Patients were eligible for inclusion if they were admitted with onset of symptoms within 24 hours. Estimation of 25(OH)D level was done at presentation. The patients were stratified by vitamin D status, >30 as vitamin D sufficient, vitamin D 20-20.9 as insufficient and finally vitamin D<20 as deficient. Multivariate logistic regression analysis revealed that out of the desired 7 variables, smoking, hypertension and low serum vitamin D were found independent predictors for acute stroke with ORs being 1.44, 4.23 and 2.39 respectively. Vitamin D deficiency represents an important risk factor for acute stroke and it might play a causal role in the development adverse events associated with stroke.Medicine Today 2018 Vol.30(1): 34-37

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A170 VITAMIN D IN IBD PATIENTS – A RETROSPECTIVE REVIEW

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.169 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 35-36

Author(s):

R A MacMillan ◽

T Ponich

Keyword(s):

Vitamin D ◽

Bone Density ◽

Disease Severity ◽

Regression Coefficient ◽

Serum Vitamin ◽

Vitamin D Supplementation ◽

Serum Vitamin D ◽

Mayo Score ◽

Vitamin D Levels ◽

Low Serum

Abstract Background Vitamin D is a critical factor in bone remodelling, calcium absorption and may promote anti-inflammatory cytokines in the gut. Inflammatory bowel disease (IBD) is associated with a reduction in serum Vitamin D levels and a chronic inflammatory state, both of which are strong risk factors for bone density loss affecting IBD patients. Despite European and North American IBD maintenance guidelines for Vitamin D monitoring and bone density scans, there are limited North American investigations into factors influencing serum Vitamin D levels in the IBD patient population specifically. Aims We investigated whether patient demographics, disease severity indexes and/or inflammatory markers were linked to low serum Vitamin D levels in our IBD patients. We also established the extent of Vitamin D serum deficiencies and supplementation rates in our IBD patients. Methods A retrospective chart review of a single clinician’s practice at London Health Science Centre, Victoria Hospital, over the past 20 months, was performed to: 1) assess the frequency of low serum 25-OH Vitamin D (25-OH D) in the IBD patient population and 2) determine whether patient disease severity was linked to lower 25-OH D levels. A multivariate regression analysis was performed assessing Crohn’s Disease (CD) or Ulcerative Colitis (UC) patient factors: age, sex, disease duration, seasonality, current pharmacologic treatments, past surgeries, CD Activity Index, UC Mayo score, C-reactive protein, and fecal calprotectin (Fcal) level. Results 175 IBD patients had at least one 25-OH D measurement with 71 patients actively on Vitamin D therapy. Of UC and CD patients who were not on Vitamin D therapy, 63% (17/27) and 79% (61/77) were 25-OH D deficient, respectively. 25-OH D levels in the CD population was associated with Vitamin D supplementation (regression coefficient [RC] 23.99, 95% confidence interval [CI] 14.54 to 33.45), summer season ([RC] 9.90, [CI] 0.56 to 19.24), and past bowel resection ([RC] -10.61, [CI] -20.48 to -0.76). 25-OH D levels in the UC population was associated with Vitamin D supplementation (regression coefficient [RC] 47.23, 95% confidence interval [CI] 27.62 to 66.83), and Mayo severity scores ([RC] -23.01, [CI] -41.82 to -4.20). Fcal (78 patients) was inversely associated with 25-OH D levels but the trend was not significant. Conclusions Overall, 25-OH D levels were lower in both the UC and CD patient populations relative to the already deficient Canadian population. However, IBD patients are responsive to Vitamin D supplementation. Tools with more objective evidence of disease severity such as UC Mayo score and fcal should be prioritized for identifying the IBD population requiring supplementation. Funding Agencies None

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