New Variants of the Cytochrome P450 2R1 (CYP2R1) Gene in Individuals with Severe Vitamin D-Activating Enzyme 25(OH)D Deficiency

Background: Vitamin D is a fat-soluble cholesterol derivative found in two forms, vitamin D2, and vitamin D3. Cytochrome P450 2R1 (CYP2R1) encoded by the CYP2R1 gene is the major hydroxylase that activates vitamin D by catalyzing the formation of 25-hydroxyvitamin D (25(OH)D). Methods: We collected 89 (100%) subjects, 46 of which (51.69%) had a documented severe deficiency of 25(OH)D (<10 ng/mL) and 43 (48.31%) in the control group with documented optimum levels of 25(OH)D (>30 ng/mL). We performed Sanger sequencing of three selected fragments of the CYP2R1 gene (Ch11: 14878000–14878499; Ch11: 14880058–14880883 and Ch11: 14885321–14886113) that affect the binding of substrates to this enzyme and analyzed the possible involvement of genetic variation in these regions with an increased risk of vitamin D deficiency in healthy Polish individuals. Results: Two substitutions were found within the three fragments. Bioinformatic analysis suggested that one of these (NC_000011.10: g.14878291G>A) may influence the structure and function of CYP2R1. Conclusions: Variant NC_000011.10: g.14878291G>A may have a perturbing effect on heme binding in the active site of CYP2R1 and on the function of 25-hydroxylase and probably affects the concentration of 25(OH)D in vivo. We intend to perform functional verification in a larger patient population to confirm and extend these results.

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Five salmon dinners per week were not sufficient to prevent the reduction in serum vitamin D in autumn at 60° north latitude: a randomised trial

British Journal Of Nutrition ◽

10.1017/s0007114519002964 ◽

2019 ◽

Vol 123 (4) ◽

pp. 419-427 ◽

Cited By ~ 2

Author(s):

Marianne Bratlie ◽

Ingrid V. Hagen ◽

Anita Helland ◽

Øivind Midttun ◽

Arve Ulvik ◽

...

Keyword(s):

Vitamin D ◽

Fish Intake ◽

Control Group ◽

Serum Concentrations ◽

Hydroxyvitamin D ◽

Western Norway ◽

Increased Risk ◽

25 Hydroxyvitamin D ◽

High Fish ◽

North Latitude

AbstractLow serum concentrations of several vitamins have been linked to increased risk of diseases including insulin resistance and type 2 diabetes (T2D). Fish is a good source of several vitamins, and the prevalence of T2D is low in populations with high fish intake. The aim of the present study was to investigate the effects of high fish intake on vitamins in serum from adults in autumn in South-Western Norway at 60° north latitude. In this randomised clinical trial, sixty-three healthy participants with overweight/obesity consumed 750 g/week of either cod (n 22) or salmon (n 22) as five weekly dinners or were instructed to continue their normal eating habits but avoid fish intake (Control group, n 19) for 8 weeks. The estimated vitamin D intake was significantly increased in the Salmon group when compared with the Cod group (P = 6·3 × 10−4) and with the Control group (P = 3·5 × 10−6), with no differences between groups for estimated intake of vitamins A, B1, B2, B3, B6, B9, C and E. Serum 25-hydroxyvitamin D3 concentration was decreased in all groups after 8 weeks; however, the reduction in the Salmon group was significantly smaller compared with the Cod group (P = 0·013) and the Control group (P = 0·0060). Cod and salmon intake did not affect serum concentrations of the other measured vitamins. The findings suggest that 750 g/week of salmon was not sufficient to prevent a decrease in serum 25-hydroxyvitamin D3 in autumn in South-Western Norway in adults with overweight/obesity.

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Evaluation of Maternal Serum 25-Hydroxyvitamin D Levels in Patients with Hyperemesis Gravidarum at Early Gestational Weeks

Eurasian Journal of Family Medicine ◽

10.33880/ejfm.2020090302 ◽

2020 ◽

Vol 9 (3) ◽

pp. 123-130

Author(s):

Burcu Kayılı ◽

Muhammet Ali Oruç ◽

Yasemin Alan ◽

Murat Alan ◽

Deniz Can Öztekin

Keyword(s):

Vitamin D ◽

Pregnant Women ◽

Vitamin D Deficiency ◽

Hyperemesis Gravidarum ◽

Control Group ◽

Hydroxyvitamin D ◽

Severe Deficiency ◽

Vitamin D Levels ◽

25 Hydroxyvitamin D ◽

The Mean

Aim: The aim of this study was to compare vitamin D levels between pregnant women with hyperemesis gravidarum before 12 weeks of gestation and healthy pregnant women at similar ages. Methods: Sixty pregnancies with hyperemesis gravidarum and 60 age compatible healthy pregnancies applied to our facility were included in the study. Demographic characteristics, maternal thyroid function tests and 25-Hydroxyvitamin D levels were evaluated. Student t test was used for the variables with normal distribution and Mann-Whitney U test was used to analyze the variables without normal distribution. Results: Only one pregnant woman had normal vitamin D levels (>30ng/ml), whereas 71 patients had deficiency (10-30 ng/ml), and 48 had severe deficiency (<10 ng/ml). The mean vitamin D level of the total 120 pregnancies was 11.9±5.00 ng/ml (9.92±3.67 ng/ml in case group, 13.88±5.38 ng/ml in control group). The mean value of vitamin D was found to be significantly lower in hyperemesis gravidarum. 45% (n=27) of the pregnant women had vitamin D deficiency, whereas 55% (n=33) of them had severe deficiency. Free T3 and T4 levels were significantly higher than the control group, and thyroid-stimulating hormone level was significantly lower. Conclusion: Vitamin D levels of pregnant women with hyperemesis gravidarum were significantly lower. Vitamin D deficiency should be considered in patients with hyperemesis gravidarum. Keywords: pregnancy, hyperemesis gravidarum, Vitamin D deficiency

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Low 25(OH)D Level Is Associated with Severe Course and Poor Prognosis in COVID-19

Nutrients ◽

10.3390/nu13093021 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3021

Author(s):

Tatiana L. Karonova ◽

Alena T. Andreeva ◽

Ksenia A. Golovatuk ◽

Ekaterina S. Bykova ◽

Anna V. Simanenkova ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Severe Disease ◽

Fatal Outcome ◽

Hydroxyvitamin D ◽

Severe Vitamin ◽

Severe Deficiency ◽

Moderate Disease ◽

Increased Risk ◽

Discharged Patients

We evaluated associations between serum 25-hydroxyvitamin D [25(OH)D] level and severity of new coronavirus infection (COVID-19) in hospitalized patients. We assessed serum 25(OH)D level in 133 patients aged 21–93 years. Twenty-five (19%) patients had severe disease, 108 patients (81%) had moderate disease, and 18 (14%) patients died. 25(OH)D level ranged from 3.0 to 97.0 ng/mL (median, 13.5 [25%; 75%, 9.6; 23.3] ng/mL). Vitamin D deficiency was diagnosed in 90 patients, including 37 with severe deficiency. In patients with severe course of disease, 25(OH)D level was lower (median, 9.7 [25%; 75%, 6.0; 14.9] ng/mL), and vitamin D deficiency was more common than in patients with moderate course (median, 14.6 [25%; 75%, 10.6; 24.4] ng/mL, p = 0.003). In patients who died, 25(OH)D was 9.6 [25%; 75%, 6.0; 11.5] ng/mL, compared with 14.8 [25%; 75%, 10.1; 24.3] ng/mL in discharged patients (p = 0.001). Severe vitamin D deficiency was associated with increased risk of COVID-19 severity and fatal outcome. The threshold for 25(OH)D level associated with increased risk of severe course was 11.7 ng/mL. Approximately the same 25(OH)D level, 10.9 ng/mL, was associated with increased risk of mortality. Thus, most COVID-19 patients have vitamin D deficiency; severe vitamin D deficiency is associated with increased risk of COVID-19 severity and fatal outcome.

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Smoking during pregnancy reduces vitamin D levels in a Finnish birth register cohort

Public Health Nutrition ◽

10.1017/s1368980018003932 ◽

2019 ◽

Vol 23 (7) ◽

pp. 1273-1277 ◽

Cited By ~ 1

Author(s):

A Inkeri Lokki ◽

Jenni Heikkinen-Eloranta ◽

Hanna Öhman ◽

Seppo Heinonen ◽

Heljä-Marja Surcel ◽

...

Keyword(s):

Vitamin D ◽

Sun Exposure ◽

First Trimester ◽

Population Based ◽

Control Group ◽

Skeletal Health ◽

Smoking During Pregnancy ◽

Hydroxyvitamin D ◽

Increased Risk ◽

Vitamin D Levels

AbstractObjectiveMaternal vitamin D level in pregnancy may have implications for both the mother and fetus. Deficiency of vitamin D has been linked to several pregnancy complications and fetal skeletal health. Smoking has been associated with reduced serum level of the vitamin D metabolite, 25-hydroxyvitamin D (25(OH)D).DesignA nested case–control study within the Finnish Maternity Cohort, a population-based cohort which includes first-trimester sera from 98 % of pregnancies in Finland since 1987. The selection consisted of women with uncomplicated pregnancies. We studied serum concentration of 25(OH)D in 313 non-smoking and forty-six self-reported smoking pregnant women.SettingWe hypothesize that pregnant smokers may have an increased risk of low 25(OH)D levels especially during winter months.ParticipantsA control group from an unpublished pregnancy complication study consisting of 359 uncomplicated pregnancies. Individuals who reported that they do not smoke were considered ‘non-smokers’ (n 313) and those who reported continued smoking after the first trimester of pregnancy were considered ‘smokers’ (n 46).ResultsSmokers had significantly lower levels of 25(OH)D irrespective of sampling time (P<0·0001). Furthermore, during the low sun-exposure season, only 14 % of smokers met the guideline level of 40 nmol/l for serum 25(OH)D in comparison with 31 % of non-smokers.ConclusionsExpectant mothers who smoke have an increased risk of vitamin D deficiency during low sun-exposure months in northern regions. Further studies are needed to assess the associated risks for maternal and fetal health as well as possible long-term implications for the infant.

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Plasma 25-Hydroxyvitamin D Levels and Fracture Risk in a Community-Based Cohort of Elderly Men in Sweden

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-2699 ◽

2010 ◽

Vol 95 (6) ◽

pp. 2637-2645 ◽

Cited By ~ 63

Author(s):

Håkan Melhus ◽

Greta Snellman ◽

Rolf Gedeborg ◽

Liisa Byberg ◽

Lars Berglund ◽

...

Keyword(s):

Vitamin D ◽

Uv Light ◽

Winter Season ◽

Community Dwelling ◽

Reference Level ◽

Blood Levels ◽

Elderly Men ◽

Hydroxyvitamin D ◽

Increased Risk ◽

25 Hydroxyvitamin D

Abstract Context: Blood levels of 25-hydroxyvitamin D [25(OH)D] is the generally accepted indicator of vitamin D status, but no universal reference level has been reached. Objective: The objective of the study was to determine the threshold at which low plasma 25(OH)D levels are associated with fractures in elderly men and clarify the importance of low levels on total fracture burden. Design and Participants: In the Uppsala Longitudinal Study of Adult Men, a population-based cohort (mean age, 71 yr, n = 1194), we examined the relationship between 25(OH)D and risk for fracture. Plasma 25(OH)D levels were measured with high-pressure liquid chromatography-mass spectrometry. Setting: The study was conducted in the municipality of Uppsala in Sweden, a country with a high fracture incidence. Main Outcome Measure: Time to fracture was measured. Results: During follow-up (median 11 yr), 309 of the participants (26%) sustained a fracture. 25(OH)D levels below 40 nmol/liter, which corresponded to the fifth percentile of 25(OH)D, were associated with a modestly increased risk for fracture, multivariable-adjusted hazard ratio 1.65 (95% confidence interval 1.09–2.49). No risk difference was detected above this level. Approximately 3% of the fractures were attributable to low 25(OH)D levels in this population. Conclusions: Vitamin D insufficiency is not a major cause of fractures in community-dwelling elderly men in Sweden. Despite the fact that cutaneous synthesis of previtamin D during the winter season is undetectable at this northern latitude of 60°, only one in 20 had 25(OH)D levels below 40 nmol/liter, the threshold at which the risk for fracture started to increase. Genetic adaptations to limited UV light may be an explanation for our findings.

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Vitamin D signalling in adipose tissue

British Journal Of Nutrition ◽

10.1017/s0007114512003285 ◽

2012 ◽

Vol 108 (11) ◽

pp. 1915-1923 ◽

Cited By ~ 161

Author(s):

Cherlyn Ding ◽

Dan Gao ◽

John Wilding ◽

Paul Trayhurn ◽

Chen Bing

Keyword(s):

Vitamin D ◽

Adipose Tissue ◽

Vitamin D Deficiency ◽

Vitamin D Metabolites ◽

Hydroxyvitamin D ◽

The Metabolic Syndrome ◽

Prevalence Of Obesity ◽

Adipose Tissue Development ◽

And Function

Vitamin D deficiency and the rapid increase in the prevalence of obesity are both considered important public health issues. The classical role of vitamin D is in Ca homoeostasis and bone metabolism. Growing evidence suggests that the vitamin D system has a range of physiological functions, with vitamin D deficiency contributing to the pathogenesis of several major diseases, including obesity and the metabolic syndrome. Clinical studies have shown that obese individuals tend to have a low vitamin D status, which may link to the dysregulation of white adipose tissue. Recent studies suggest that adipose tissue may be a direct target of vitamin D. The expression of both the vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) genes has been shown in murine and human adipocytes. There is evidence that vitamin D affects body fat mass by inhibiting adipogenic transcription factors and lipid accumulation during adipocyte differentiation. Some recent studies demonstrate that vitamin D metabolites also influence adipokine production and the inflammatory response in adipose tissue. Therefore, vitamin D deficiency may compromise the normal metabolic functioning of adipose tissue. Given the importance of the tissue in energy balance, lipid metabolism and inflammation in obesity, understanding the mechanisms of vitamin D action in adipocytes may have a significant impact on the maintenance of metabolic health. In the present review, we focus on the signalling role of vitamin D in adipocytes, particularly the potential mechanisms through which vitamin D may influence adipose tissue development and function.

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COVID-19 Disease Severity and Death in Relation to Vitamin D Status among SARS-CoV-2-Positive UAE Residents

Nutrients ◽

10.3390/nu13051714 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1714

Author(s):

Habiba AlSafar ◽

William B. Grant ◽

Rafiq Hijazi ◽

Maimunah Uddin ◽

Nawal Alkaabi ◽

...

Keyword(s):

Vitamin D ◽

United Arab Emirates ◽

Blood Levels ◽

Vitamin D Status ◽

Hospital Visit ◽

Serum Samples ◽

Hydroxyvitamin D ◽

Increased Risk ◽

Multiethnic Population ◽

25 Hydroxyvitamin D

Insufficient blood levels of the neurohormone vitamin D are associated with increased risk of COVID-19 severity and mortality. Despite the global rollout of vaccinations and promising preliminary results, the focus remains on additional preventive measures to manage COVID-19. Results conflict on vitamin D’s plausible role in preventing and treating COVID-19. We examined the relation between vitamin D status and COVID-19 severity and mortality among the multiethnic population of the United Arab Emirates. Our observational study used data for 522 participants who tested positive for SARS-CoV-2 at one of the main hospitals in Abu Dhabi and Dubai. Only 464 of those patients were included for data analysis. Demographic and clinical data were retrospectively analyzed. Serum samples immediately drawn at the first hospital visit were used to measure serum 25-hydroxyvitamin D [25(OH)D] concentrations through automated electrochemiluminescence. Levels < 12 ng/mL were significantly associated with higher risk of severe COVID-19 infection and of death. Age was the only other independent risk factor, whereas comorbidities and smoking did not contribute to the outcomes upon adjustment. Sex of patients was not an important predictor for severity or death. Our study is the first conducted in the UAE to measure 25(OH)D levels in SARS-CoV-2-positive patients and confirm the association of levels < 12 ng/mL with COVID-19 severity and mortality.

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Complete Genome Sequence of an Efficient Vitamin D3-Hydroxylating Bacterium, Pseudonocardia autotrophica NBRC 12743

Microbiology Resource Announcements ◽

10.1128/mra.01105-18 ◽

2018 ◽

Vol 7 (12) ◽

Cited By ~ 1

Author(s):

Keitaro Yoshida ◽

Yoshiaki Yasutake ◽

Tomohiro Tamura

Keyword(s):

Vitamin D ◽

Cytochrome P450 ◽

Genome Sequence ◽

Vitamin D3 ◽

Complete Genome Sequence ◽

Complete Genome ◽

Commercial Production ◽

Content Type ◽

Hydroxyvitamin D

Pseudonocardia autotrophica NBRC 12743 contains a cytochrome P450 vitamin D3 hydroxylase, and it is used as a biocatalyst for the commercial production of hydroxyvitamin D3, a valuable compound for medication. Here, we report the complete genome sequence of P. autotrophica NBRC 12743, which could be useful for improving the productivity of hydroxyvitamin D3.

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Association of serum vitamin D levels and transient tachypnea of newborn: a case control study

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20171526 ◽

2017 ◽

Vol 4 (3) ◽

pp. 827 ◽

Cited By ~ 1

Author(s):

Gurmeet Singh ◽

Reena Sood ◽

Gursharan Singh Narang ◽

Harnoorjit Kaur Brar ◽

Amanjeet Kaur Bagga

Keyword(s):

Vitamin D ◽

Serum Vitamin ◽

Transient Condition ◽

Control Group ◽

Term Neonates ◽

Serum Vitamin D ◽

Increased Risk ◽

Vitamin D Levels ◽

Control Study ◽

Structured Questionnaire

Background: Transient tachypnea of newborn (TTN) is a common cause of respiratory distress in newborns with estimated incidence of 1-2% of all newborns. Although a self-limiting transient condition but it may cause severe morbidities. This study was conducted to find association of serum vitamin D levels in neonates who develop TTN as compared to normal healthy neonates.Methods: With thorough history with structured questionnaire and lab tests, serum vitamin D levels of 45 neonates who develop TTN were compared with 56 healthy neonates in control group.Results: Out of 45 neonates who develop TTN 39(86.7%) were deficient in vitamin D as compared to control group where 33(58.9%) out of 56 healthy neonates were deficient in vitamin D.Conclusions: Lower vitamin D levels at birth in term neonates is associated with increased risk of developing TTN and vitamin D may have a role in its pathogenesis.

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25-hydroxyvitamin D effect on cancer colon: Is visceral obesity the link?

10.21203/rs.3.rs-373290/v1 ◽

2021 ◽

Author(s):

Mohamed M. Aboelnaga ◽

Engy Mossad Aboelnaga ◽

Abdullah Nahed ◽

Mostafa El Shaer

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Visceral Obesity ◽

Control Group ◽

Visceral Adiposity Index ◽

Group 13 ◽

Hydroxyvitamin D ◽

Inflammatory Status ◽

Obesity And Cancer ◽

Cancer Côlon

Abstract Background: low 25-hydroxyvitamin have been identified in pathogenesis of colorectal cancer (CRC) with survival affection. Visceral fat tissue predisposes to chronic inflammation and release of growth factors that mediate colonic neoplasia.Aim of the work: to evaluate effect of vitamin D status and visceral obesity on cancer colon and to report the possible link between vitamin D and visceral obesity in those patients. Patients & Methods: Our patients were distributed in two groups; group 1 included cancer colon cases (no= 60) and 2nd group included control cases (no= 40). Clinical, anthropometric and pathological data were collected. Calculation of body mass index, visceral adiposity index (VAI) and detection of Vitamin D (25 OHD) serum level were performed to compare between groups. Results: There were significant differences in VAI and level of 25 OHD between both groups(P=0.011). We found significant higher prevalence of vitamin d deficiency in patient’ group [32 (53.3%) versus control group 13 (32.5%)]. There was a significant lower mean of VAI in vitamin D deficient patients versus non deficient cases (P=0.024). A significant different means of VAI and Vitamin D in patients’ group with different TNM stages. As higher stages associated with lower level of Vitamin D (P=0.027) and higher VAI (P=0.031)Conclusion: The vitamin D may augment the inflammatory status in visceral obesity which reported to be involved in tumourgenesis of cancer colon. Vitamin D deficiency may be a mediator between obesity and cancer and associated with higher tumour stage.

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