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      Hyperhomocysteinemia is Associated with Inflammation, Bone Resorption, Vitamin B12 and Folate Deficiency and MTHFR C677T Polymorphism in Postmenopausal Women with Decreased Bone Mineral Density

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          Abstract

          Osteoporosis is an age-related bone disease, affecting mainly postmenopausal women, characterized by decreased bone mineral density (BMD) and consequent risk of fractures. Homocysteine (Hcy), a sulfur-aminoacid whose serum level is regulated by methylenetrahydrofolate reductase (MTHFR) activity and vitamin B12 and folate as cofactors, is a risk factor for inflammatory diseases. Literature data concerning the link between Hcy and osteoporosis are still debated. The aim of our study was to assess the relationship among Hcy and BMD, inflammation, vitamin status and bone turnover in postmenopausal osteoporosis. In 252 postmenopausal women, BMD was measured by dual-energy X-ray absorptiometry (DXA). In addition to serum Hcy, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and bone turnover markers (bone alkaline phosphatase-BAP, osteocalcin-OC, C-terminal telopeptide of type I collagen (CTX), vitamin deficiencies and MTHFR-C677T polymorphism were evaluated. Hcy, inflammation, bone resorption markers and prevalence of C677T polymorphism were higher, whereas vitamin D, B12, folate, and bone formation markers were lower in women with decreased BMD compared to those with normal BMD. Our results suggest a significant association between Hcy, BMD and inflammation in postmenopausal osteoporosis. The regulation of Hcy overproduction and the modulation of the inflammatory substrate could represent additional therapeutic approaches for osteoporosis prevention.

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          Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases.

          Siaw-Cheok Liew, Esha das Gupta (2015)
          The Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with various diseases (vascular, cancers, neurology, diabetes, psoriasis, etc) with the epidemiology of the polymorphism of the C677T that varies dependent on the geography and ethnicity. The 5,10-Methylenetetrahydrofolate reductase (MTHFR) locus is mapped on chromosome 1 at the end of the short arm (1p36.6). This enzyme is important for the folate metabolism which is an integral process for cell metabolism in the DNA, RNA and protein methylation. The mutation of the MTHFR gene which causes the C677T polymorphism is located at exon 4 which results in the conversion of valine to alanine at codon 222, a common polymorphism that reduces the activity of this enzyme. The homozygous mutated subjects have higher homocysteine levels while the heterozygous mutated subjects have mildly raised homocysteine levels compared with the normal, non-mutated controls. Hyperhomocysteinemia is an emerging risk factor for various cardiovascular diseases and with the increasing significance of this polymorphism in view of the morbidity and mortality impact on the patients, further prevention strategies and nutritional recommendations with the supplementation of vitamin B12 and folic acid which reduces plasma homocysteine level would be necessary as part of future health education. This literature review therefore focuses on the recent evidence-based reports on the associations of the MTHFR C677T polymorphism and the various diseases globally.
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            Prevalence of Hyperhomocysteinemia in China: A Systematic Review and Meta-Analysis

            Boyi Yang, Shujun Fan, Xueyuan Zhi … (2014)
            Hyperhomocysteinemia (HHcy, total homocysteine concentrations > 15 μmol/L) has been associated with increased risk of many diseases. A systematic review was performed to summarize the prevalence of HHcy in China. We searched multiple international and Chinese scientific databases for relevant literature, and further manually screened reference lists and corresponded with original authors. Pooled prevalence of HHcy was calculated using random effects model. Subgroup analysis, meta-regression and sensitivity analysis were also performed. A total of 36 studies consisting 60,754 subjects (57.3% male; age range, 3–97 years) were finally included. The overall pooled prevalence of HHcy was 27.5%. Geographically, the prevalence was high in north areas, intermediate in central areas, and low in south areas, and was higher in inland versus coastal areas. The prevalence increased with age and was significantly higher in men than in women. Rural residents had a slightly higher HHcy prevalence than urban residents, and the studies conducted during 2006 to 2012 presented a higher HHcy prevalence than those during 1990 to 2005. In summary, the prevalence of HHcy in China is high, particularly in northern populations, the inlanders, males, and the elderly. Homocysteine-lowering strategies are necessary to reduce this highly preventable disorder.
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              Hyperhomocysteinemia as a Risk Factor and Potential Nutraceutical Target for Certain Pathologies

              Caterina Tinelli, Antonella Di Pino, Elena Ficulle … (2019)
              Hyperhomocysteinemia is recognized as a risk factor for several diseases, including cardiovascular and neurological conditions. Homocysteine (HCys) is a key metabolite involved in the biosynthesis and metabolism of methionine (Met), which plays a pivotal role in the physiological cell's life cycle. The biochemistry of Met is finely regulated by several enzymes that control HCys concentration. Indeed, balanced activity among the enzymes is essential for the cell's well-being, while its malfunction could raise HCys concentration which can lead to the onset of several pathological conditions. The HCys concentration increase seems to be caused mainly by the widely diffused polymorphisms of several enzymes. Nowadays, a blood test can easily detect elevated concentrations of HCys, referred to as Hyperhomocysteinemia (HHCys). Prolonged exposure to this condition can lead to the onset of cardiovascular disease and can lead to the development of atherosclerosis, stroke, inflammatory syndromes like osteoporosis and rheumatism, as well as neuronal pathologies including Alzheimer's and Parkinson's diseases. In this review, we analyzed the literature of several pathological conditions in which the molecular pathways of HHCys are involved. Interestingly, several observations indicate that the calibrated assumption of correct doses of vitamins such as folic acid, vitamin B6, vitamin B12, and betaine may control HHCys-related conditions.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Environ Res Public Health
                Journal ID (iso-abbrev): Int J Environ Res Public Health
                Journal ID (publisher-id): ijerph
                Title: International Journal of Environmental Research and Public Health
                Publisher: MDPI
                ISSN (Print): 1661-7827
                ISSN (Electronic): 1660-4601
                Publication date (Electronic): 15 June 2020
                Publication date (Print): June 2020
                Volume: 17
                Issue: 12
                Electronic Location Identifier: 4260
                Affiliations
                [1 ]Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; maddalena.sirufo@ 123456gmail.com (M.M.S.); lia.ginaldi@ 123456cc.univaq.it (L.G.)
                [2 ]Allergy and Clinical Immunology Unit, Center for the diagnosis and treatment of Osteoporosis, AUSL 04, 64100 Teramo, Italy
                [3 ]Pneumology Unit, AUSL 04, 64100 Teramo, Italy; cristina.nocelli@ 123456aslteramo.it
                [4 ]Department of Legal and Social Sciences, University of Chieti-Pescara, 65127 Pescara, Italy; lara.fontanella@ 123456unich.it
                Author notes
                [* ]Correspondence: demartinis@ 123456univaq.it ; Tel.: +39-0861-429548; Fax: +39-0861-211395
                Article
                Publisher ID: ijerph-17-04260
                DOI: 10.3390/ijerph17124260
                PMC ID: 7345373
                PubMed ID: 32549258
                SO-VID: 1af2104b-6e8a-4a97-86a5-2c44441c86da
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 12 May 2020
                Date accepted : 12 June 2020
                Categories
                Subject: Article

                ScienceOpen disciplines: Public health
                Keywords: osteoporosis,hyperhomocysteinemia,inflammation,vitamin d,bone,vitamin b12,folate,mthfr,postmenopausal women,bone mineral density
                Data availability:
                ScienceOpen disciplines: Public health
                Keywords: osteoporosis, hyperhomocysteinemia, inflammation, vitamin d, bone, vitamin b12, folate, mthfr, postmenopausal women, bone mineral density

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