scholarly journals 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

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.

scholarly journals The causal effect of serum vitamin D concentration on COVID-19 susceptibility, severity and hospitalization traits: a Mendelian randomization study

2021 ◽  
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

AbstractBackgroundEvidence supporting the role of vitamin D in the coronavirus disease 2019 (COVID-19) pandemic remains controversial.MethodsWe 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 median 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.ResultsWe 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.ConclusionsOur 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 therefore 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.

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

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2608
Author(s):  
Sara Tomei ◽  
Parul Singh ◽  
Rebecca Mathew ◽  
Valentina Mattei ◽  
Mathieu Garand ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Vitamin ◽  
Vitamin D Supplementation ◽  
Nucleotide Polymorphisms ◽  
Vitamin D Status ◽  
Vdr Gene ◽  
Individual Level ◽  
Serum Vitamin D ◽  
Vitamin D Levels

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.

scholarly journals Could vitamin D reduce obesity-associated inflammation? Observational and Mendelian randomization study

2020 ◽  
Vol 111 (5) ◽  
pp. 1036-1047 ◽  
Author(s):  
Saranya Palaniswamy ◽  
Dipender Gill ◽  
N Maneka De Silva ◽  
Estelle Lowry ◽  
Jari Jokelainen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Acute Phase Proteins ◽  
Causal Effect ◽  
Vitamin D Supplementation ◽  
Inflammatory Biomarkers ◽  
Intercellular Adhesion Molecule ◽  
Hs Crp

ABSTRACT Background Obesity is associated with inflammation but the role of vitamin D in this process is not clear. Objectives We aimed to assess the associations between serum 25-hydroxyvitamin D [25(OH)D], BMI, and 16 inflammatory biomarkers, and to assess the role of vitamin D as a potential mediator in the association between higher BMI and inflammation. Methods Northern Finland Birth Cohort 1966 (NFBC1966) 31-y data on 3586 individuals were analyzed to examine the observational associations between BMI, 25(OH)D, and 16 inflammatory biomarkers. Multivariable regression analyses and 2-sample regression-based Mendelian randomization (MR) mediation analysis were performed to assess any role of vitamin D in mediating a causal effect of BMI on inflammatory biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1), high sensitivity C-reactive protein (hs-CRP), and α1-acid glycoprotein (AGP)] for which observational associations were detected. For MR, genome-wide association study summary results ranging from 5163 to 806,834 individuals were used for biomarkers, 25(OH)D, and BMI. Findings were triangulated with a literature review of vitamin D supplementation trials. Results In NFBC1966, mean BMI (kg/m2) was 24.8 (95% CI: 24.7, 25.0) and mean 25(OH)D was 50.3 nmol/L (95% CI: 49.8, 50.7 nmol/L). Inflammatory biomarkers correlated as 4 independent clusters: interleukins, adhesion molecules, acute-phase proteins, and chemokines. BMI was positively associated with 9 inflammatory biomarkers and inversely with 25(OH)D (false discovery rate < 0.05). 25(OH)D was inversely associated with sICAM-1, hs-CRP, and AGP, which were positively associated with BMI. The MR analyses showed causal association of BMI on these 3 inflammatory biomarkers. There was no observational or MR evidence that circulating 25(OH)D concentrations mediated the association between BMI and these 3 inflammatory markers. Review of randomized controlled trials (RCTs) supported our findings showing no impact of vitamin D supplementation on inflammatory biomarkers. Conclusions The findings from our observational study and causal MR analyses, together with data from RCTs, do not support a beneficial role of vitamin D supplementation on obesity-related inflammation.

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

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.

Evaluation of the hormonal and biochemical changes in obese and non-obese PCOS Iraqi women before and after vitamin D supplementation

2019 ◽  
Vol 9 (o3) ◽  
Author(s):  
Suaad Muhssen Ghazi ◽  
Fatin Shallal Farhan
Keyword(s):  
Vitamin D ◽  
Serum Vitamin ◽  
Follicular Development ◽  
High Body Mass Index ◽  
Vitamin D Supplementation ◽  
The Body ◽  
Obese People ◽  
Serum Vitamin D ◽  
Before And After ◽  
Granulose Cells

Vitamin D deficiency is common in women with polycystic ovarian syndrome. Vitamin D plays an important physiologic role in reproductive functions of ovarian follicular development and luteinization through altering anti-müllerian hormone signaling, follicular stimulating hormone activity and progesterone production in human granulose cells. Vitamin D is precipitated in adipose fat tissues, making it notable to be used for the body as a result; obese people with high body mass index are already highly expected to have low levels of serum vitamin D.

SUBLINGUAL VITAMIN D3 DRUG THERAPY IN VITAMIN D DEFICIENCY PATIENTS AT PRAVARA RURAL HOSPITAL

2019 ◽  
pp. 18-20
Author(s):  
Sanjeeva Kumar Goud T ◽  
Rahul Kunkulol
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Vitamin D3 ◽  
Serum Vitamin ◽  
Cross Sectional ◽  
Serum Vitamin D ◽  
Significant Difference ◽  
Before And After

The present study was aimed to study the effect of Sublingual Vitamin D3 on Serum Vitamin D level in Vitamin D deficiency patients. This was a cross-sectional and interventional study. All the Vitamin D deficiency patients of age 18-60years and either gender, willing to participate in the study were included. Patients who had greater than 20 ng/ml were excluded from the study. The total number of participants in our study was 200, out of these 111 males and 89 females, the mean age in our study was 51.07 ± 7.39Yrs. All volunteers were given sublingual vitamin D3 (60,000IU) in six doses every fifteen days of follow up for 3 months. The subject’s serum 25(OH)D levels were estimated before and after the treatment of sublingual vitamin D3. There was a statistically significant difference in serum vitamin D3 level before 16.61±6.71 ng/ml and after 35.80±7.80 ng/ml after treatment with Sublingual Vitamin D3. Six doses of 60,000IU of Vitamin D3 sublingual route having improved the role of serum 25(OH)D levels in the treatment of Vitamin D3 deficiency patients.Keywords: Vitamin D3; Sublingual route

scholarly journals Retrospective analysis of the role of serum vitamin D in early rheumatic disease

Rheumatology ◽  
2014 ◽  
Vol 54 (2) ◽  
pp. 374-375 ◽  
Author(s):  
F. A. H. Cooles ◽  
A. G. Pratt ◽  
D. W. Lendrem ◽  
W.-F. Ng ◽  
T. J. Aspray ◽  
...  
Keyword(s):  
Vitamin D ◽  
Rheumatic Disease ◽  
Retrospective Analysis ◽  
Serum Vitamin ◽  
Serum Vitamin D

Low serum vitamin D, statin associated muscle symptoms, vitamin D supplementation

2017 ◽  
Vol 256 ◽  
pp. 125-127 ◽  
Author(s):  
Charles J. Glueck ◽  
Kevin Lee ◽  
Marloe Prince ◽  
Alexander Milgrom ◽  
Frini Makadia ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Vitamin ◽  
Vitamin D Supplementation ◽  
Serum Vitamin D ◽  
Low Serum

Serum Vitamin D: Correlates of Baseline Concentration and Response to Supplementation in VITAL-DKD

2021 ◽  
Author(s):  
Cora M Best ◽  
Leila R Zelnick ◽  
Kenneth E Thummel ◽  
Simon Hsu ◽  
Christine Limonte ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Parent Compound ◽  
Serum Vitamin ◽  
Vitamin D Supplementation ◽  
Total Serum ◽  
P Value ◽  
Hydroxyvitamin D ◽  
Serum Vitamin D ◽  
Vitamin D3 Supplementation

Abstract Context The effect of daily vitamin D supplementation on the serum concentration of vitamin D (the parent compound) may offer insight into vitamin D disposition. Objective To assess the total serum vitamin D response to vitamin D3 supplementation and whether it varies according to participant characteristics. To compare results with corresponding results for total serum 25-hydroxyvitamin D (25(OH)D), which is used clinically and measured in supplementation trials. Design Exploratory study within a randomized trial. Intervention 2,000 International Units of vitamin D3 per day (or matching placebo). Setting Community-based. Participants 161 adults (mean ± SD age 70 ± 6 years; 66% males) with type 2 diabetes. Main Outcome Measures Changes in total serum vitamin D and total serum 25(OH)D concentrations from baseline to year 2. Results At baseline, there was a positive, nonlinear relation between total serum vitamin D and total serum 25(OH)D concentrations. Adjusted effects of supplementation were a 29.2 (95% CI: 24.3, 34.1) nmol/L increase in serum vitamin D and a 33.4 (95% CI: 27.7, 39.2) nmol/L increase in serum 25(OH)D. Among those with baseline 25(OH)D < 50 compared with ≥ 50 nmol/L, the serum vitamin D response to supplementation was attenuated (15.7 vs 31.2 nmol/L; interaction p-value = 0.02), whereas the serum 25(OH)D response was augmented (47.9 vs 30.7 nmol/L; interaction p-value = 0.05). Conclusions Vitamin D3 supplementation increases total serum vitamin D and 25(OH)D concentrations with variation according to baseline 25(OH)D, which suggests that 25-hydroxylation of vitamin D3 is more efficient when serum 25(OH)D concentration is low.

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

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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