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      Gender difference in relationship between serum ferritin and 25-hydroxyvitamin D in Korean adults

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          Abstract

          Background

          The present study was conducted to assess the gender difference in the relationship between serum ferritin and 25-hydroxyvitamin D [25(OH)D] in Korean adults.

          Methods

          A total of 5,147 adults (2,162 men, 1,563 premenopausal women, and 1,422 postmenopausal women) aged ≥ 20 years from the Korean National Health and Nutrition Examination Survey (KNHANES) data (2012) were analyzed. A covariance test adjusted for covariates was performed for serum ferritin levels in relation to vitamin D status (vitamin D deficiency, 25(OH)D < 10.0 ng/mL; vitamin D insufficiency, 25(OH)D ≥ 10.0, < 20.0 ng/mL; vitamin D sufficiency, 25(OH)D ≥ 20.0 ng/mL).

          Results

          The key study results were as follows: First, in men, in terms of serum ferritin levels by serum 25(OH)D level after adjusting for age, smoking, alcohol drinking, regular exercise, SBP, DBP, WM. TC, TGs, HDL-C, FPG, Hb, Hct, MCV, and Fe, serum ferritin levels were inversely increased with the increasing of serum 25(OH)D level ( P = 0.012). Second, in premenopausal women, after adjusting for related variables, serum ferritin levels were increased with the increasing of serum 25(OH)D level ( P = 0.003). Third, in postmenopausal women, after adjusting for related variables, serum ferritin levels were not significantly increased with the increasing of serum 25(OH)D level ( P = 0.456).

          Conclusion

          Serum 25(OH)D level was inversely associated with the serum ferritin levels in men, but was positively associated with the serum ferritin levels in premenopausal women, and was not associated with the serum ferritin levels in postmenopausal women.

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          Most cited references40

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          The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis.

          Altered vitamin D and calcium homeostasis may play a role in the development of type 2 diabetes mellitus (type 2 DM). EVIDENCE ACQUISITION AND ANALYSES: MEDLINE review was conducted through January 2007 for observational studies and clinical trials in adults with outcomes related to glucose homeostasis. When data were available to combine, meta-analyses were performed, and summary odds ratios (OR) are presented. Observational studies show a relatively consistent association between low vitamin D status, calcium or dairy intake, and prevalent type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM prevalence, 0.36 (0.16-0.80) among nonblacks for highest vs. lowest 25-hydroxyvitamin D; metabolic syndrome prevalence, 0.71 (0.57-0.89) for highest vs. lowest dairy intake]. There are also inverse associations with incident type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM incidence, 0.82 (0.72-0.93) for highest vs. lowest combined vitamin D and calcium intake; 0.86 (0.79-0.93) for highest vs. lowest dairy intake]. Evidence from trials with vitamin D and/or calcium supplementation suggests that combined vitamin D and calcium supplementation may have a role in the prevention of type 2 DM only in populations at high risk (i.e. glucose intolerance). The available evidence is limited because most observational studies are cross-sectional and did not adjust for important confounders, whereas intervention studies were short in duration, included few subjects, used a variety of formulations of vitamin D and calcium, or did post hoc analyses. Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism.
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            Regulation of iron metabolism by hepcidin.

            Hepcidin, a peptide hormone made in the liver, is the principal regulator of systemic iron homeostasis. Hepcidin controls plasma iron concentration and tissue distribution of iron by inhibiting intestinal iron absorption, iron recycling by macrophages, and iron mobilization from hepatic stores. Hepcidin acts by inhibiting cellular iron efflux through binding to and inducing the degradation of ferroportin, the sole known cellular iron exporter. Synthesis of hepcidin is homeostatically increased by iron loading and decreased by anemia and hypoxia. Hepcidin is also elevated during infections and inflammation, causing a decrease in serum iron levels and contributing to the development of anemia of inflammation, probably as a host defense mechanism to limit the availability of iron to invading microorganisms. At the opposite side of the spectrum, hepcidin deficiency appears to be the ultimate cause of most forms of hemochromatosis, either due to mutations in the hepcidin gene itself or due to mutations in the regulators of hepcidin synthesis. The emergence of hepcidin as the pathogenic factor in most systemic iron disorders should provide important opportunities for improving their diagnosis and treatment.
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              In vivo evidence for a novel pathway of vitamin D₃ metabolism initiated by P450scc and modified by CYP27B1.

              We define previously unrecognized in vivo pathways of vitamin D(3) (D3) metabolism generating novel D3-hydroxyderivatives different from 25-hydroxyvitamin D(3) [25(OH)D3] and 1,25(OH)(2)D3. Their novel products include 20-hydroxyvitamin D(3) [20(OH)D3], 22(OH)D3, 20,23(OH)(2)D3, 20,22(OH)(2)D3, 1,20(OH)(2)D3, 1,20,23(OH)(3)D3, and 17,20,23(OH)(3)D3 and were produced by placenta, adrenal glands, and epidermal keratinocytes. We detected the predominant metabolite [20(OH)D3] in human serum with a relative concentration ∼20 times lower than 25(OH)D3. Use of inhibitors and studies performed with isolated mitochondria and purified enzymes demonstrated involvement of the steroidogenic enzyme cytochrome P450scc (CYP11A1) as well as CYP27B1 (1α-hydroxylase). In placenta and adrenal glands with high CYP11A1 expression, the predominant pathway was D3 → 20(OH)D3 → 20,23(OH)(2)D3 → 17,20,23(OH)(3)D3 with further 1α-hydroxylation, and minor pathways were D3 → 25(OH)D3 → 1,25(OH)(2)D3 and D3 → 22(OH)D3 → 20,22(OH)(2)D3. In epidermal keratinocytes, we observed higher proportions of 22(OH)D3 and 20,22(OH)(2)D3. We also detected endogenous production of 20(OH)D3, 22(OH) D3, 20,23(OH)(2)D3, 20,22(OH)(2)D3, and 17,20,23(OH)(3)D3 by immortalized human keratinocytes. Thus, we provide in vivo evidence for novel pathways of D3 metabolism initiated by CYP11A1, with the product profile showing organ/cell type specificity and being modified by CYP27B1 activity. These findings define the pathway intermediates as natural products/endogenous bioregulators and break the current dogma that vitamin D is solely activated through the sequence D3 → 25(OH)D3 → 1,25(OH)(2)D3.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                31 May 2017
                2017
                : 12
                : 5
                : e0177722
                Affiliations
                [1 ]Department of Dental Hygiene, College of Health Science, Kangwon National University, Samcheok-si, Gangwon-do, South Korea
                [2 ]Department of Radiological Science, Hanlyo University, Gwangyang-si, jeollanam-do, South Korea
                [3 ]Department of Health Science Graduate School, Chosun University, Gwangju, South Korea
                [4 ]Department of Biomedical Laboratory Science, Kwangyang Health College, Gwangyang-si, Jeollanam-do, South Korea
                [5 ]Department of Nursing, Christian College of Nursing, Gwangju, South Korea
                [6 ]Department of Biomedical Laboratory Science, Hanlyo University, Gwangyang-si, Jeollanam-do, South Korea
                University of Alabama at Birmingham, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: JMS HY.

                • Data curation: JMS YSY.

                • Formal analysis: YSY KSL.

                • Investigation: KSL NYB.

                • Methodology: JMS YSY KSL NYB MYG HY.

                • Writing – original draft: JMS HY.

                • Writing – review & editing: JMS NYB MYG HY.

                Author information
                http://orcid.org/0000-0002-4741-9664
                Article
                PONE-D-17-09209
                10.1371/journal.pone.0177722
                5451000
                28562685
                776f7e1e-deca-44ab-a058-eb0f80354683
                © 2017 Seong et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 8 March 2017
                : 2 May 2017
                Page count
                Figures: 0, Tables: 5, Pages: 13
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Physical sciences
                Chemistry
                Chemical compounds
                Organic compounds
                Vitamins
                Vitamin D
                Physical sciences
                Chemistry
                Organic chemistry
                Organic compounds
                Vitamins
                Vitamin D
                Biology and Life Sciences
                Biochemistry
                Proteins
                Protein Complexes
                Ferritin
                Biology and Life Sciences
                Biochemistry
                Proteins
                Protein Complexes
                Ferritin
                Serum Ferritin Levels
                Biology and life sciences
                Nutrition
                Nutritional deficiencies
                Vitamin D deficiency
                Medicine and health sciences
                Nutrition
                Nutritional deficiencies
                Vitamin D deficiency
                Biology and Life Sciences
                Nutrition
                Diet
                Alcohol Consumption
                Medicine and Health Sciences
                Nutrition
                Diet
                Alcohol Consumption
                Medicine and Health Sciences
                Hematology
                Anemia
                Iron Deficiency Anemia
                Medicine and Health Sciences
                Endocrinology
                Endocrine Physiology
                Insulin Resistance
                Biology and Life Sciences
                Physiology
                Endocrine Physiology
                Insulin Resistance
                Medicine and Health Sciences
                Physiology
                Endocrine Physiology
                Insulin Resistance
                Biology and Life Sciences
                Biochemistry
                Hormones
                Estrogens
                Custom metadata
                The official website of KNHANES ( http://knhanes.cdc.go.kr) is currently operating an English-language information homepage. The data of the respective year are available to everyone at the free of charge. If the applicant enters simple subscription process and his email address in the official website of KNHANES, the data of the respective year can download to free of charge. If additional information is required, the readers can contact Su Yeon Park at sun4070@ 123456korea.kr .

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