scholarly journals Associations between Genetic Variants in the Vitamin D Metabolism Pathway and Severity of COVID-19 among UAE Residents

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3680
Author(s):  
Fatme Al-Anouti ◽  
Mira Mousa ◽  
Spyridon N. Karras ◽  
William B. Grant ◽  
Zainab Alhalwachi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
United Arab Emirates ◽  
Genetic Variants ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Potential Risk Factors ◽  
25 Hydroxyvitamin D

Vitamin D has many effects on cells in the immune system. Many studies have linked low vitamin D status with severity of COVID-19. Genetic variants involved in vitamin D metabolism have been implicated as potential risk factors for severe COVID-19 outcomes. This study investigated how genetic variations in humans affected the clinical presentation of COVID-19. In total, 646 patients with SARS-CoV-2 infection were divided into two groups: noncritical COVID-19 (n = 453; 70.12%) and a critical group (n = 193; 29.87%). Genotype data on the GC, NADSYN1, VDR, and CYP2R1 genes along with data on serum 25-hydroxyvitamin D levels were compiled in patients admitted to a major hospital in the United Arab Emirates between April 2020 and January 2021. We identified 12 single-nucleotide polymorphisms associated with the critical COVID-19 condition: rs59241277, rs113574864, rs182901986, rs60349934, and rs113876500; rs4944076, rs4944997, rs4944998, rs4944979, and rs10898210; and rs11574018 and rs11574024. We report significant associations between genetic determinants of vitamin D metabolism and COVID-19 severity in the UAE population. Further research needed to clarify the mechanism of action against viral infection in vitamin D deficiency. These variants could be used with vaccination to manage the spread of SARS-CoV-2 and could be particularly valuable in populations in which vitamin D deficiency is common.

scholarly journals Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D–Related Genetic Variants

2017 ◽  
Vol 102 (8) ◽  
pp. 2941-2949 ◽  
Author(s):  
Rebecca J Moon ◽  
Nicholas C Harvey ◽  
Cyrus Cooper ◽  
Stefania D’Angelo ◽  
Elizabeth M Curtis ◽  
...  
Keyword(s):  
Vitamin D ◽  
Group Analysis ◽  
Additive Model ◽  
Nucleotide Polymorphisms ◽  
Vitamin D Metabolism ◽  
Single Nucleotide ◽  
White Ethnicity ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Cholecalciferol Supplementation

Abstract Context Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation. Objective To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation. Design Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation. Setting Hospital antenatal clinics. Participants In total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped. Interventions 1000 IU/d cholecalciferol from 14 weeks of gestation until delivery. Main Outcome Measure 25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [β represents the change in 25(OH)D per additional common allele]. Results Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [β = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P < 0.004]. In contrast, rs10741657 (CYP2R1) (β = −5.2 nmol/L; 95% CI, −8.2 to −2.2 nmol/L; P = 0.001) and rs2282679 (GC) (β = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; P = 0.01) were associated with achieved 25(OH)D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not. Conclusions Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity.

Vitamin D3 metabolism in a pig strain with pseudo vitamin D-deficiency rickets, type I

1987 ◽  
Vol 115 (3) ◽  
pp. 345-352 ◽  
Author(s):  
Reinhard Kaune ◽  
Johein Harmeyer
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Type I ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Before And After ◽  
25 Hydroxyvitamin D ◽  
Deficiency Rickets ◽  
Clinical Healing

Abstract. Vitamin D metabolism was studied in the 'Hannover Pig', a strain which suffers from pseudo vitamin D-deficiency rickets, type I. Animals of this strain are known to be devoid of renal 25-hydroxyvitamin D3-1α-hydroxylase and -24-hydroxylase activities. Pigs with florid rickets and hypocalcaemia were treated with single im injections of 0.25 to 1.25 mg of vitamin D3, doses that have been shown in previous studies to be effective in producing transient healing of rachitic symptoms. The levels of vitamin D3 and its most relevant physiological metabolites in plasma were estimated at intervals before and after this vitamin D3 treatment. Vitamin D3 rose from 14.8 ± 8.1 to 364 ± 190 nmol/l (mean ± sd) 2 to 3 days post injectionem, 25-hydroxyvitamin D3 from 131.0 ± 46.2 to 1068 ± 160 nmol/l within 7 days post injectionem. The 1α,25-dihydroxyvitamin D3 concentration in plasma was elevated from 73.9 ± 25.0 to 281 ± 168 pmol/l 2 to 3 days post injectionem and declined continually from that time. 24R,25-dihydroxyvitamin D3 and 25S,26-dihydroxyvitamin D3 levels after treatment showed different responses in different animals being either elevated or unchanged. Clinical healing of the pigs with these doses of vitamin D3 was attributed to the transient rise of 1α,25-dihydroxyvitamin D3 in plasma. It was assumed that 1α,25-dihydroxyvitamin D3 synthesis takes place under these circumstances in extrarenal tissues.

scholarly journals Vitamin D Metabolism and Guidelines for Vitamin D Supplementation

2020 ◽  
Vol 41 (3) ◽  
pp. 103-126
Author(s):  
Indra Ramasamy
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Vitamin D Supplementation ◽  
Vitamin D Status ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Response Data ◽  
Vitamin D Intake ◽  
25 Hydroxyvitamin D ◽  
Significant Health

Vitamin D is essential for bone health and is known to be involved in immunomodulation and cell proliferation. Vitamin D status remains a significant health issue worldwide. However, there has been no clear consensus on vitamin D deficiency and its measurement in serum, and clinical practice of vitamin D deficiency treatment remains inconsistent. The major circulating metabolite of vitamin D, 25-hydroxyvitamin D (25(OH)D), is widely used as a biomarker of vitamin D status. Other metabolic pathways are recognised as important to vitamin D function and measurement of other metabolites may become important in the future. The utility of free 25(OH)D rather than total 25(OH)D needs further assessment. Data used to estimate the vitamin D intake required to achieve a serum 25(OH)D concentration were drawn from individual studies which reported dose-response data. The studies differ in their choice of subjects, dose of vitamin D, frequency of dosing regimen and methods used for the measurement of 25(OH)D concentration. Baseline 25(OH)D, body mass index, ethnicity, type of vitamin D (D2 or D3) and genetics affect the response of serum 25(OH)D to vitamin D supplementation. The diversity of opinions that exist on this topic are reflected in the guidelines. Government and scientific societies have published their recommendations for vitamin D intake which vary from 400–1000 IU/d (10–25 µg/d) for an average adult. It was not possible to establish a range of serum 25(OH)D concentrations associated with selected non-musculoskeletal health outcomes. To recommend treatment targets, future studies need to be on infants, children, pregnant and lactating women.

scholarly journals Serum 25-Hydroxyvitamin D Concentrations and Major Depression: A Mendelian Randomization Study

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1987 ◽  
Author(s):  
Karl Michaëlsson ◽  
Håkan Melhus ◽  
Susanna Larsson
Keyword(s):  
Vitamin D ◽  
Major Depression ◽  
Mendelian Randomization ◽  
Vitamin D Insufficiency ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Single Nucleotide ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
25 Hydroxyvitamin D

Whether vitamin D insufficiency is a contributing cause of depression remains unclear. We assessed whether serum 25-hydroxyvitamin D (S-25OHD) concentrations, the clinical marker of vitamin D status, were associated with major depression using Mendelian randomization. We used summary statistics data for six single-nucleotide polymorphisms significantly associated with S-25OHD concentrations in the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) consortium and the corresponding data for major depression (n = 59,851 cases and 113,154 controls) from the Psychiatric Genomics Consortium. Genetically predicted S-25OHD concentrations were not associated with major depression. The odds ratio per genetically predicted one standard deviation decrease in S-25OHD concentrations was 1.02 (95% confidence interval 0.97–1.08; p = 0.44). The results of this study indicate that genetically lowered S-25OHD concentrations are not associated with increased risk of developing major depression.

Depressed Serum 25-Hydroxyvitamin D Levels Increase Hospital Stay and Alter Glucose Homeostasis in First-ever Ischemic Stroke

2019 ◽  
Vol 16 (4) ◽  
pp. 340-347
Author(s):  
Yuge Wang ◽  
Yanqiang Wang ◽  
Bingjun Zhang ◽  
Yinyao Lin ◽  
Sha Tan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Ischemic Stroke ◽  
Hospital Stay ◽  
Functional Outcome ◽  
Vitamin D Deficiency ◽  
Glucose Homeostasis ◽  
Clinical Severity ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Deficiency Group

Background and Objective: Vitamin D deficiency is internationally recognized among the potentially modifiable risk factors for ischemic cardio-cerebrovascular diseases. However, the association between vitamin D deficiency and stroke morbidity or mortality remains insufficiently known. Our aim is to investigate their relevance to 25-hydroxyvitamin D [25(OH) D] levels and clinical severity and outcome after 3 months in first-ever ischemic stroke. Methods: Retrospective analysis of 356 consecutive patients in first-ever ischemic stroke between 2013 and 2015. Serum 25(OH) D levels were measured at baseline. Stroke severity was assessed at admission using the National Institutes of Health Stroke Scale (NIHSS) score. Functional outcome after 3 months of onset was evaluated using the modified Rankin scale (mRS). Results: Among the 356 enrolled patients, HbA1c was higher in insufficiency/deficiency group than that in the sufficiency group (6.3 ± 1.7 vs. 5.9 ± 1.1, p =0.015). The hospital stay was longer in insufficiency/deficiency group than that in the sufficiency group (11 (8-17) vs. 9.5 (7-13), p = 0.035). There was a significant inversed trend between serum 25(OH) D levels and hospital stay (OR 0.960, P = 0.031), using logistic regression. Conclusions: 25(OH)D levels are associated with glucose homeostasis, 25(OH) D contributes to increase the length of hospital stay. Low serum 25-OHD level is an independent predictor for hospital stay in first-ever ischemic stroke. Vitamin D deficiency did not predict functional outcome in the span of 3 months.

scholarly journals Association of serum 25-hydroxyvitamin D with metabolic syndrome and type 2 diabetes: a one sample Mendelian randomization study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Xiao ◽  
Jingyi Lv ◽  
Shiyu Wang ◽  
Yang Zhou ◽  
Lunwen Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Mendelian Randomization ◽  
Middle Aged ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Randomization Analysis

Abstract Background Vitamin D deficiency has been associated with type 2 diabetes (T2D) and metabolic syndrome (MS) and its components. However, it is unclear whether a low concentration of vitamin D is the cause or consequence of these health conditions. Thus, this study aimed to evaluate the association of vitamin D concentrations and its genetic risk scores (GRSs) with MS and its component diseases, such as T2D, in middle-aged and elderly participants from rural eastern China. Methods A subset of 2393 middle-aged and elderly individuals were selected from 70,458 participants of the Nantong Chronic Diseases Study of 2017–2018 in China. We used two 25-hydroxyvitamin D (25[OH]D) synthesis single-nucleotide polymorphisms (SNPs) (DHCR7-rs12785878 and CYP2R1-rs10741657) and two 25(OH) D metabolism SNPs (GC-rs2282679 and CYP24A1-rs6013897) for creating GRSs, which were used as instrumental variables to assess the effect of genetically lowered 25(OH) D concentrations on MS and T2D based on the Wald ratio. F statistics were used to validate that the four SNPs genetically determined 25(OH) D concentrations. Results Compared to vitamin D sufficient individuals, individuals with vitamin D insufficiency had an odds ratio (OR [95% confidence interval {CI}]) of MS of 1.30 (1.06–1.61) and of T2D of 1.32 (1.08–1.64), individuals with vitamin D deficiency had an ORs (95% CI) of MS of 1.50 (1.24–1.79) and of T2D of 1.47 (1.12–1.80), and those with vitamin D severe deficiency had an ORs (95% CI) of MS of 1.52 (1.29–1.85) and of T2D of 1.54 (1.27–1.85). Mendelian randomization analysis showed a 25-nmol/L decrease in genetically instrumented serum 25(OH) D concentrations using the two synthesis SNPs (DHCR7 and CYP2R1 genes) associated with the risk of T2D and abnormal diastolic blood pressure (DBP) with ORs of 1.10 (95%CI: 1.02–1.45) for T2D and 1.14 (95%CI: 1.03–1.43) for DBP. Conclusions This one sample Mendelian randomization analysis shows genetic evidence for a causal role of lower 25(OH) D concentrations in promoting of T2D and abnormal DBP in middle-aged and elderly participants from rural China.

Serum 25-Hydroxyvitamin D Concentrations and Cardiometabolic Biomarkers in Chinese Rural Population

2021 ◽  
Vol 53 (02) ◽  
pp. 105-111
Author(s):  
Dongdong Zhang ◽  
Cheng Cheng ◽  
Yan Wang ◽  
Yuan Xue ◽  
Yiming Liu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Rural Population ◽  
Density Lipoprotein ◽  
Cubic Spline ◽  
Lipoprotein Cholesterol ◽  
Linear Regression Models ◽  
Hydroxyvitamin D ◽  
Linear Association ◽  
25 Hydroxyvitamin D

AbstractThere is a paucity of data on the relation between serum 25-hydroxyvitamin D [25(OH)D] concentration and cardiometabolic biomarkers in the Chinese population. To comprehensively and quantitatively examine the association of 25(OH)D and cardiometabolic traits, we conducted a cross-sectional study in the Chinese rural population. Serum 25(OH)D and eight cardiometabolic biomarkers were measured in 1714 individuals from Henan province, China. Scatter plot was used to visualize the distribution and correlation of 25(OH)D and cardiometabolic indicators. Moreover, multivariate linear regressions and restricted cubic spline (RCS) functions were performed to examine the quantitative association between the serum 25(OH)D and cardiometabolic parameters. The median serum 25(OH)D level was 19.94 ng/ml in all participants, with an estimated 50.12% presenting vitamin D deficiency. Serum 25(OH)D level showed significantly modest association with cardiometabolic parameters (p<0.05) except for diastolic blood pressure (r=0.03, p=0.22). Multiple linear regression models showed that 25(OH)D concentration was positively associated with high-density lipoprotein cholesterol (HDL-C) and negatively associated with low-density lipoprotein cholesterol (LDL-C) and fasting serum glucose (GLU). The results of restricted cubic spline models indicated a positively linear association of 25(OH)D with HDL-C (p for overall<0.001, p for nonlinearity=0.191) and a negatively linear association with GLU (p for overall=0.024, p for nonlinearity=0.095). Overall, vitamin D deficiency was very common among Chinese rural population living near the 34 degrees north latitude. Besides, there were significant association between 25(OH)D concentrations and cardiometabolic biomarkers including HDL-C and GLU levels. Future longitudinal studies and randomized trials are warranted to clarify the causal relationship.

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