In silico analysis of the rs1803909 polymorphysis of the ANXA2 gene expressed in peripheral blood monocytes and its association with human osteoporosis
DOI:
https://doi.org/10.33448/rsd-v11i1.24356Keywords:
Blood circulation; Blood; Calcium; Osteoporosis; Polymorphism, single nucleotide.Abstract
The objective was to evaluate the possible morphofunctional and protein stability alterations resulting from Tyrosine amino acid changes by a Histidine at position 269, as well as to correlate with the physiological function of the protein and its probable association with human osteoporosis. Through an in silico analysis based on the information available in the NCBI dbSNP (amino acid change and position) and UNIPROT (sequence in the protein) databases. The impacts of the Y269H modification were analyzed from the tools SIFT, Align-GVGD, SNAP and PROVEAN (function and structure), and PolyPhen-2 (nature of the change). In addition, MuPRO tool (stability changes in the protein) were also used. In silico analysis of the rs1803909 polymorphism demonstrated functional alteration (SIFT tool, Score= 0). As well as, it is estimated that amino acid exchange may be related to damaging alterations (PolyPhen-2, Score= 0.993) and associated with modifications in protein function (PROVEAN, Score= -4.015). In addition, structural (Align-GVGD, Score= 83.33, Class C65) and functional (SNAP, Score= 57) impacts were observed. Complementarily, decreased protein stability arising from Y269H alteration was observed by MuPRO tool, ∆∆G= -1.6731749. However, morphofunctional alterations may be connected to damaging processes and the decreased stability of the protein, thus hindering its action. Furthermore, understanding the morphofunctional and stability changes of rs1803909 may aid in the search for early diagnostic genetic and molecular markers for osteoporosis in humans.
References
Adzhubei, I. A., et al. (2010). A method and server for predicting damaging missense mutations. Nat Methods, 7(4): 248-249.
Blakely, R. D. (2005). Overview: a rare opportunity or just one less reason to be depressed. Neuron, 48, 701-2.
Bromberg, Y. & Rost, B. (2007). SNAP: predict effect of non-synonymous polymorphisms on function. Nucleic Acids Res. 35(11): 3823-3835.
Brownstein, C., et al. (2004). Annexin II mediates plasminogen-dependent matrix invasion by human monocytes: Enhanced expression by macrophages. Blood., 103, 317–324.
Cesarman, G. M., Guevara, C. A., Hajjar, K. A. (1994). An endothelial cell receptor for plasminogen/tissue plasminogen activator (t-PA). II. Annexin II-mediated enhancement of t-PA-dependent plasminogen activation. J. Biol. Chem., 269, 21198–21203.
Cheng, J., Randall, A., Baldi, P. (2006). Prediction of protein stability changes for single-site mutations using support vector machines. Proteins, 62(4): 1125-1132.
Choi, Y. & Chan A. P. (2015). PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels. Bioinformatics, 31(16): 2745-2747.
Chorley, B. N., et al. (2008). Discovery and verification of functional single nucleotide polymorphisms in regulatory genomic regions: current and developing technologies. Mutat Res, 659, 147-57.
Cohen-Solal, M. E., et al. (1993). Peripheral monocyte culture supernatants of menopausal women can induce bone resorption: involvement of cytokines. J. Clin. Endocrinol. Metab., 77, 1648-1653.
Cohen-Solal, M. E., et al. (1998). Increased bone resorbing activity of peripheral monocyte culture supernatants in elderly women. J. Clin. Endocrinol. Metab., 83, 1687-1690.
Coughlan, T., & Dockery, F. (2014). Osteoporosis and fracture risk in older people. Clinical medicine, 14, 187–191.
Dassah, M., et al. (2009). The Endothelial Cell Annexin A2 System and Vascular Fibrinolysis. Gen. Physiol. Biophys., 28, 20–28.
De Jong, M. C., et al. (2010). CD44 Expression Predicts Local Recurrence After Radiotherapy In Larynx Cancer. Clin. Cancer Res., 16, 5329-5338.
Deng, F. Y., et al. (2008). Proteomic analysis of circulating monocytes in Chinese premenopausal females with extremely discordant bone mineral density. Proteomics., 8, 4259-4272.
Deng, F. Y., et al. (2011). Peripheral blood monocyte-expressed ANXA2 gene is involved in pathogenesis of osteoporosis in humans. Molecular & cellular proteomics: MCP, 10, M111.011700.
Drysdale, C. M., et al. (2000). Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci., USA, 97, 10483-8.
Falcone, D. J., et al. (2001). Plasminogen-mediated matrix invasion and degradation by macrophages is dependent on surface expression of annexin II. Blood., 97, 777-784.
Farber, C. R. (2010). Identification of a gene module associated with BMD through the integration of network analysis and genome-wide association data. J. Bone Miner. Res., 25, 2359-2367.
Ferraz, C. P.; Nolasco, R. W. M.; Amaral, P. A. S. & Pereira, L. C. (2021). Osteoporosis and oral health: literature review. Research, Society and Development, 10(15), e275101522930. https://doi.org/10.33448/rsd-v10i15.22930
Frazer, K. A., et al. (2007). International HapMap Consortium. A second generation human haplotype map of over 3.1 million SNPs. Nature, 449, 851-61.
Gerke, V., Creutz, C. E., Moss, S. E. (2005). Annexins: Linking Ca2+ signalling to membrane dynamics. Nat. Rev. Mol. Cell Biol., 6, 449–461.
Hajjar, K. A. & Acharya, S. S. (2000). Annexin II and Regulation of Cell Surface Fibrinolysis. Ann. N. Y. Acad. Sci., 902, 265–271.
Hajjar, K. A. (2015). The Biology of Annexin A2: From Vascular Fibrinolysis to Innate Immunity. Trans. Am. Clin. Climatol. Assoc., 126, 144–155.
Hajjar, K. A.; Jacovina, A. T.; Chacko, J. (1994). An endothelial cell receptor for plasminogen/tissue plasminogen activator. I. Identity with annexin II. J. Biol. Chem., 269, 21191–21197.
Hedhli, N. D. J., et al. (2012). The annexin A2/S100A10 system in health and disease: emerging paradigms. J.Biomed.Biotechnol. p. 4062-73.
Karg, K., et al. (2011). The serotonin transporter promoter variant (5-HTTLPR), stress, and depression metaanalysis revisited: evidence of genetic moderation. Arch Gen Psychiatry, 68, 444-54.
Kesisis, G., et al. (2010). Biological markers in breast cancer prognosis and treatment. J. Buon., 15, 447-454.
Kuo, Y. B., et al. (2011). Identification of Phospholipid Scramblase 1 as a biomarker and it's prognostic value for Colorectal Cancer. Mol. Med., 17, 41-47.
Lane, J. M. & Nydick, M. (1999). Osteoporosis: Current modes of prevention and treatment. J Am Acad Ortho Surg, 7, 19-31.
Li, F., et al. (2005). Annexin II stimulates RANKL expression through MAPK. J. Bone Miner. Res., 20, 1161-1167.
Liao, P-Y. & Lee, K. H. (2010). From SNPs to functional polymorphism: the in sight into biotechnology applications. Biochem Eng J, 49, 149-58.
Liu, Y. Z., et al. (2005). A novel pathophysiological mechanism for osteoporosis suggested by an in vivo gene expression study of circulating monocytes. J. Biol. Chem., 280, 29011-29016.
Lu, G., et al. (2006). Cloning and characterization of the annexin II receptor on human marrow stromal cells. J. Biol. Chem., 281, 30542-30550.
Mathe, E., et al. (2006). Abordagens computacionais para prever o efeito biológico de mutações missense de p53: uma comparação de três métodos baseados em análise de sequência. Nucleic Acids Res. 34 (5): 1317–25.
Mcvoy, L. A. & Kew, R. R. (2005). CD44 and Annexin A2 Mediate the C5a Chemotactic Cofactor Function of the Vitamin D Binding Protein. J. Immunol., 175, 4754–4760.
Menaa, C., et al. (1999). Annexin II increases osteoclast formation by stimulating the proliferation of osteoclast precursors in human marrow cultures. J. Clin. Invest., 103, 1605-1613.
Mota, P. H. R., et al. (2021). The influence of osteoporosis on implant dentistry. Research, Society and Development, 10(15), e82101522976. https://doi.org/10.33448/rsd-v10i15.22976
Ng, P. C. & Henikoff S. (2003). SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 31(13): 3812-3814.
Pacifici, R. (1996). Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J. Bone Miner. Res., 11, 1043-1051.
Parfitt, A. M. (2001). Skeletal heterogeneity and the purposes of bone remodelling: implications for the understanding of osteoporosis. In: Marcus R. Zfeldman D. Kelsey J. Osteoporosis. Academic Press, San Diego, 433-444.
Parfitt, A. M., et al. (1996). A new model for the regulation of bone resorption, with particular reference to the effects of bisphosphonates. J. Bone Miner. Res., 11, 150-159.
Ramalho, A. C. R., et al. (2000). Por Que Estrógeno e Raloxifeno Melhoram a Densidade Mineral Óssea? Mecanismo de Ação do Estrógeno e de Um Modulador Seletivo do Receptor de Estrógeno (SERM) no Osso. Arq. Bras. Endocrinol. Metab. 44(6), 471-482.
Rankin, C. R., et al. (2013). Annexin A2 Regulates β1 Integrin Internalization and Intestinal Epithelial Cell Migration. J. Biol. Chem., 288, 15229–15239.
Rescher, U. & Gerke, V. (2004). Annexins unique membrane binding proteins with diverse functions. J. Cell Sci., 117, 2631–2639.
Rezende, R. B. & Teodoro, L. (2021). Impacto Do Polimorfismo RS121913578 do Gene Mrt Associado ao Câncer de Tireoide: Impact of the RS121913578 Polymorphism of the Mrt Gene Associated with Thyroid Cancer. Archives of Health, 2(4), 1101–1104.
Rezende, R. B. (2021). Hemodynamic Dysfunctions in COVID-19 Patients. Research, Society and Development, 10(12), e111101220323. https://doi.org/10.33448/rsd-v10i12.20323
Riggs, B. L. & Melton, L. J. (1983). Evidence for two distinct syndromes of involutional osteoporosis. Am J Med, 75, 899-901.
Roodman, G. D. (2006). Regulation of osteoclast differentiation. Ann. N.Y. Acad. Sci., 1068, 100-109.
Sadee, W., et al. (2011). Pharmacogenomics of the RNA world: structural RNA polymorphisms in drug therapy. Clin Pharmacol Ther, 89, 355-65.
Takahashi, S., et al. (1994). Cloning and identification of annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption. J. Biol. Chem., 269, 28696-28701.
Tavtigian, S. V., et al. (2006). An Analysis of Unclassified Missense Substitutions in Human BRCA1. Cancro Familiar. 5 (1): 77–88.
Xu, X. H., et al. (2010). Molecular genetic studies of gene identification for osteoporosis: the 2009 update. Endocr. Rev., 31, 447-505.
Zhang, X., et al. (2005). Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Neuron, 45, 11-16.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Rubens Barbosa Rezende; Larissa Teodoro Rabi
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
