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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

      Submit here before July 31, 2024

      About Blood Purification: 3.0 Impact Factor I 5.6 CiteScore I 0.83 Scimago Journal & Country Rank (SJR)

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      The Impact of CYP24A1 Polymorphisms on Hypertension Susceptibility

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          Abstract

          Background: Hypertension is one of the leading causes of human death and disability. CYP24A1 regulates vitamin D activity and is closely linked to hypertension. However, the relationship between CYP24A1polymorphisms and hypertension risk remains unclear. Methods: This case-control study included 503 hypertensive patients and 498 healthy controls from the Chinese Han population. The genotypes of CYP24A1polymorphisms were detected using the Agena MassARRAY method. The association between genetic variations of CYP24A1and hypertension risk was evaluated with odds ratios (OR) and 95% confidence intervals (CI) in genetic models. Results: We found that rs56229249 of CYP24A1significantlydecreased the hypertension risk in homozygote (OR 0.51, 95% CI 0.29–0.91, p = 0.022) and recessive models (OR 0.51, 95% CI 0.29–0.91, p = 0.023). Further stratification analyses indicated that hypertension risk is related to age and sex, rs2762934 polymorphism increases hypertension risk among younger subjects (<61 years), and rs1977297 influences the risk of hypertension among older subjects (≥61 years). In addition, rs2762940 is related to hypertension risk in men, and rs56229249 is a protective factor against hypertension in women. Conclusions: Our study suggests that genetic variations of the CYP24A1gene were significantly associated with susceptibility to hypertension in the Chinese population.

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          Trends in blood pressure among adults with hypertension: United States, 2003 to 2012.

          Sung Sug Yoon, Qiuping Gu, Tatiana Nwankwo … (2015)
          The aim of this study is to describe trends in the awareness, treatment, and control of hypertension; mean blood pressure; and the classification of blood pressure among US adults 2003 to 2012. Using data from the National Health and Nutrition Examination Survey 2003 to 2012, a total of 9255 adult participants aged ≥18 years were identified as having hypertension, defined as measured blood pressure ≥140/90 mm Hg or taking prescription medication for hypertension. Awareness and treatment among hypertensive adults were ascertained via an interviewer administered questionnaire. Controlled hypertension among hypertensive adults was defined as systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg. Blood pressure was categorized as optimal blood pressure, prehypertension, and stage I and stage II hypertension. Between 2003 and 2012, the percentage of adults with controlled hypertension increased (P-trend <0.01). Hypertensive adults with optimal blood pressure and with prehypertension increased from 13% to 19% and 27% to 33%, respectively (P-trend <0.01 for both groups). Among hypertensive adults who were taking antihypertensive medication, uncontrolled hypertension decreased from 38% to 30% (P-trend <0.01). Similarly, a decrease in mean systolic blood pressure was observed (P-trend <0.01); however, mean diastolic blood pressure remained unchanged. The trend in the control of blood pressure has improved among hypertensive adults resulting in a higher percentage with blood pressure at the optimal or prehypertension level and a lower percentage in stage I and stage II hypertension. Overall, mean systolic blood pressure decreased as did the prevalence of uncontrolled hypertension among the treated hypertensive population.
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            Synthesis of 1,25-dihydroxyvitamin D(3) by human endothelial cells is regulated by inflammatory cytokines: a novel autocrine determinant of vascular cell adhesion.

            Christine Stewart, Amanda C de C Williams, Ravinder Chana … (2002)
            In addition to its calciotropic function, the secosteroid 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) has potent nonclassical effects. In particular, local production of 1,25D(3) catalyzed by the enzyme 1alpha-hydroxylase (1alpha-OHase) may act as an autocrine/paracrine immunomodulatory mechanism. To investigate the significance of this in vascular tissue the expression and function of 1alpha-OHase in human endothelial cells was characterized. Immunohistochemical and in situ hybridization analyses show, for the first time, the presence of 1alpha-OHase mRNA and protein in endothelial cells from human renal arteries as well as postcapillary venules from lymphoid tissue. Reverse transcription-PCR and Western blot analyses confirmed the presence of 1alpha-OHase in primary cultures of human umbilical vein endothelial cells (HUVEC). Enzyme activity in HUVEC (318 +/- 56 fmoles 1,25(OH)(2)D(3)/hr/mg protein) increased after treatment with tumor necrosis factor-alpha (1054 +/- 166, P < 0.01), lipopolysaccharide (1381 +/- 88, P < 0.01), or forskolin (554 +/- 56, P < 0.05). Functional studies showed that exogenously added 1,25(OH)(2)D(3) or its precursor, 25-hydroxyvitamin D(3) (25(OH)D(3)), significantly decreased HUVEC proliferation after 72 h of treatment (33% and 11%, respectively). In addition, after 24 h treatment, both 1,25(OH)(2)D(3) and 25(OH)D(3) increased the adhesion of monocytic U937 cells to HUVEC (159% and 153%, respectively). These data indicate that human endothelia are able to produce active vitamin D. The rapid induction of endothelial 1alpha-OHase activity by inflammatory cytokines suggests a novel autocrine/paracrine role for the enzyme, possibly as a modulator of endothelial cell adhesion.
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              Metabolism of vitamin D3 by cytochromes P450.

              Toshiyuki Sakaki, Norio Kagawa, Keiko Yamamoto … (2005)
              The vitamin D3 25-hydroxylase (CYP27A1), 25-hydroxyvitamin D3 1alpha-hydroxylase (CYP27B1) and 1alpha,25-dihydroxyvitamin D3 24-hydroxylase (CYP24A1) are members of the cytochrome P450 superfamily, and key enzymes of vitamin D3 metabolism. Using the heterologous expression in E. coli, enzymatic properties of the P450s were recently investigated in detail. Upon analyses of the metabolites of vitamin D3 by the reconstituted system, CYP27A1 surprisingly produced at least seven forms of minor metabolites including 1alpha,25(OH)2D3 in addition to the major metabolite 25(OH)D3. These results indicated that human CYP27A1 catalyzes multiple reactions involved in the vitamin D3 metabolism. In contrast, CYP27B1 only catalyzes the hydroxylation at C-1alpha position of 25(OH)D3 and 24R,25(OH)2D3. Enzymatic studies on substrate specificity of CYP27B1 suggest that the 1alpha-hydroxylase activity of CYP27B1 requires the presence of 25-hydroxyl group of vitamin D3 and is enhanced by 24-hydroxyl group while the presence of 23-hydroxyl group greatly reduced the activity. Eight types of missense mutations in the CYP27B1 gene found in vitamin D-dependent rickets type I (VDDR-I) patients completely abolished the 1alpha-hydroxylase activity. A three-dimensional model of CYP27B1 structure simulated on the basis of the crystal structure of rabbit CYP2C5 supports the experimental data from mutagenesis study of CYP27B1 that the mutated amino acid residues may be involved in protein folding, heme-propionate binding or activation of molecular oxygen. CYP24A1 expressed in E. coli showed a remarkable metabolic processes of 25(OH)D3 and 1alpha,25(OH)2D3. Rat CYP24A1 catalyzed six sequential monooxygenation reactions that convert 1alpha,25(OH)2D3 into calcitroic acid, a known final metabolite of C-24 oxidation pathway. In addition to the C-24 oxidation pathway, human CYP24A1 catalyzed also C-23 oxidation pathway to produce 1alpha,25(OH)2D3-26,23-lactone. Surprisingly, more than 70 % of the vitamin D metabolites observed in a living body were found to be the products formed by the activities of CYP27A1, CYP27B1 and CYP24A1. The species-based difference was also observed in the metabolism of vitamin D analogs by CYP24A1, suggesting that the recombinant system for human CYP24A1 may be of great use for the prediction of the metabolism of vitamin D analogs in humans.
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                Author and article information

                Journal
                Journal ID (publisher-id): KBR
                Journal ID (nlm-ta): Kidney Blood Press Res
                Journal ID (doi): 10.1159/issn.1420-4096
                Title: Kidney and Blood Pressure Research
                Publisher: S. Karger AG
                ISSN (Print): 1420-4096
                ISSN (Electronic): 1423-0143
                Publication date Subscription-year: 2020
                Publication date (Print): January 2020
                Publication date (Electronic): 09 January 2020
                Volume: 45
                Issue: 1
                Pages: 28-37
                Affiliations
                Gerontological Center, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
                Author notes
                *Haiyu Jia, Affiliated Hospital of Inner Mongolia Medical University, No. 1 North Street of Huimin Area, Inner Mongolia, Hohhot 010059 (China), E-Mail jiahaiyu0228@163.com
                Article
                Publisher ID: 503925 Other ID: Kidney Blood Press Res 2020;45:28–37
                DOI: 10.1159/000503925
                PubMed ID: 31918428
                SO-VID: 4f57fbcb-a1d3-4ea8-8be8-343c129aa51a
                Copyright © © 2020 The Author(s) Published by S. Karger AG, Basel
                License:

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 03 June 2019
                Date accepted : 04 October 2019
                Page count
                Figures: 1, Tables: 5, Pages: 10
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: CYP24A1 ,Hypertension,Case-control study,Genetic variations,Risk
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: CYP24A1 , Hypertension, Case-control study, Genetic variations, Risk

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