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Erschienen in: Inflammation 3/2023

23.12.2022 | Original Article

Assessment of Angiopoietin-2 Single Nucleotide Polymorphism in Patients with Rheumatoid Arthritis

verfasst von: Samah Ismail Nasef, Alia Ellawindy, Aya Mohamed Askar, Asmaa AbdelKreem Hashem, Hanan Hassan Omar

Erschienen in: Inflammation | Ausgabe 3/2023

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Abstract

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that destroys joint cartilage and causes disability. Synovial inflammation, with angiogenesis, is an early event in the progression of the disease. Angiopoietin 2 (ANGPT2) is a cytokine with both inflammatory and angiogenic effects. Many genes can influence RA susceptibility and disease activity. The aim is to assess the relationship between ANGPT2 gene polymorphism (rs3020221) and RA. The study was a case-control study that included 212 RA patients and 238 age-and gender-matched healthy volunteers. RA disease activity was assessed using the Disease Activity Score 28 index. Erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and antibody to cyclic citrullinated peptide were measured. ANGPT2 rs3020221 C > T SNP genotyping was done using real-time polymerase chain reaction (PCR). The TT genotype was more frequently represented in RA patients than in healthy controls (18.9% and 7.1%, respectively, p < 0.001) and increased the chance of developing RA four-fold, as compared to other genotypes (OR = 4.00, 95% CI = 2.09–7.63) (p < 0.001). The CT genotype was associated with elevated levels of the inflammatory markers ESR and CRP in RA patients (p = 0.012 and 0.037, respectively) as well as the DAS28 ESR Score (p < 0.001). The presence of the T allele either under the dominant model (for genotypes CT and TT) or the recessive model (for the genotype TT) predicts RA disease. Assessment of ANGPT2 gene polymorphism is useful to predict the patients with susceptibility to RA. The presence of T allele increased the risk of developing RA disease by two folds.
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Literatur
1.
Zurück zum Zitat Smolen, J.S., D. Aletaha, A. Barton, G.R. Burmester, P. Emery, G.S. Firestein, et al. 2018. Rheumatoid arthritis. Nature Reviews Disease Primers 4: 18001.CrossRefPubMed Smolen, J.S., D. Aletaha, A. Barton, G.R. Burmester, P. Emery, G.S. Firestein, et al. 2018. Rheumatoid arthritis. Nature Reviews Disease Primers 4: 18001.CrossRefPubMed
2.
Zurück zum Zitat Leblond, A., Y. Allanore, and J. Avouac. 2017. Targeting synovial neoangiogenesis in rheumatoid arthritis. Autoimmunity Reviews 16 (6): 594–601.CrossRefPubMed Leblond, A., Y. Allanore, and J. Avouac. 2017. Targeting synovial neoangiogenesis in rheumatoid arthritis. Autoimmunity Reviews 16 (6): 594–601.CrossRefPubMed
3.
Zurück zum Zitat Li, Y., Y. Liu, C. Wang, W.R. Xia, J.Y. Zheng, J. Yang, et al. 2018. Succinate induces synovial angiogenesis in rheumatoid arthritis through metabolic remodeling and HIF-1α/VEGF axis. Free Radical Biology & Medicine 126: 1–14.CrossRef Li, Y., Y. Liu, C. Wang, W.R. Xia, J.Y. Zheng, J. Yang, et al. 2018. Succinate induces synovial angiogenesis in rheumatoid arthritis through metabolic remodeling and HIF-1α/VEGF axis. Free Radical Biology & Medicine 126: 1–14.CrossRef
4.
Zurück zum Zitat Wang, Y., H. Wu, and R. Deng. 2021. Angiogenesis as a potential treatment strategy for rheumatoid arthritis. European Journal of Pharmacology 910: 174500.CrossRefPubMed Wang, Y., H. Wu, and R. Deng. 2021. Angiogenesis as a potential treatment strategy for rheumatoid arthritis. European Journal of Pharmacology 910: 174500.CrossRefPubMed
5.
Zurück zum Zitat Kim, J.W., J.-S. Kong, S. Lee, S.-A. Yoo, J.H. Koh, J. Jin, et al. 2020. Angiogenic cytokines can reflect the synovitis severity and treatment response to biologics in rheumatoid arthritis. Experimental & Molecular Medicine. 52 (5): 843–853.CrossRef Kim, J.W., J.-S. Kong, S. Lee, S.-A. Yoo, J.H. Koh, J. Jin, et al. 2020. Angiogenic cytokines can reflect the synovitis severity and treatment response to biologics in rheumatoid arthritis. Experimental & Molecular Medicine. 52 (5): 843–853.CrossRef
6.
Zurück zum Zitat Khodadust, F., A. Ezdoglian, M.M. Steinz, J.R. van Beijnum, G.J.C. Zwezerijnen, G. Jansen, et al. 2022. Systematic review: targeted molecular imaging of angiogenesis and its mediators in rheumatoid arthritis. International Journal of Molecular Sciences 23 (13): 7071.CrossRefPubMedPubMedCentral Khodadust, F., A. Ezdoglian, M.M. Steinz, J.R. van Beijnum, G.J.C. Zwezerijnen, G. Jansen, et al. 2022. Systematic review: targeted molecular imaging of angiogenesis and its mediators in rheumatoid arthritis. International Journal of Molecular Sciences 23 (13): 7071.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Scholz, A., K.H. Plate, and Y. Reiss. 2015. Angiopoietin-2: A multifaceted cytokine that functions in both angiogenesis and inflammation. Annals of the New York Academy of Sciences 1347: 45–51.CrossRefPubMed Scholz, A., K.H. Plate, and Y. Reiss. 2015. Angiopoietin-2: A multifaceted cytokine that functions in both angiogenesis and inflammation. Annals of the New York Academy of Sciences 1347: 45–51.CrossRefPubMed
8.
Zurück zum Zitat Nicolini, G., F. Forini, C. Kusmic, G. Iervasi, and S. Balzan. 2019. Angiopoietin 2 signal complexity in cardiovascular disease and cancer. Life Sciences 239: 117080.CrossRefPubMed Nicolini, G., F. Forini, C. Kusmic, G. Iervasi, and S. Balzan. 2019. Angiopoietin 2 signal complexity in cardiovascular disease and cancer. Life Sciences 239: 117080.CrossRefPubMed
9.
Zurück zum Zitat Mikhaylenko, D.S., M.V. Nemtsova, I.V. Bure, E.B. Kuznetsova, E.A. Alekseeva, V.V. Tarasov, et al. 2020. Genetic polymorphisms associated with rheumatoid arthritis development and antirheumatic therapy response. International Journal of Molecular Sciences 21 (14): 4911.CrossRefPubMedPubMedCentral Mikhaylenko, D.S., M.V. Nemtsova, I.V. Bure, E.B. Kuznetsova, E.A. Alekseeva, V.V. Tarasov, et al. 2020. Genetic polymorphisms associated with rheumatoid arthritis development and antirheumatic therapy response. International Journal of Molecular Sciences 21 (14): 4911.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Scherer, H.U., T. Häupl, and G.R. Burmester. 2020. The etiology of rheumatoid arthritis. Journal of Autoimmunity 110: 102400.CrossRefPubMed Scherer, H.U., T. Häupl, and G.R. Burmester. 2020. The etiology of rheumatoid arthritis. Journal of Autoimmunity 110: 102400.CrossRefPubMed
11.
Zurück zum Zitat Viatte, S., and A. Barton. 2017. Genetics of rheumatoid arthritis susceptibility, severity, and treatment response. Seminars in Immunopathology 39 (4): 395–408.CrossRefPubMedPubMedCentral Viatte, S., and A. Barton. 2017. Genetics of rheumatoid arthritis susceptibility, severity, and treatment response. Seminars in Immunopathology 39 (4): 395–408.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Yarwood, A., T.W. Huizinga, and J. Worthington. 2016. The genetics of rheumatoid arthritis: Risk and protection in different stages of the evolution of RA. Rheumatology (Oxford) 55 (2): 199–209.CrossRefPubMed Yarwood, A., T.W. Huizinga, and J. Worthington. 2016. The genetics of rheumatoid arthritis: Risk and protection in different stages of the evolution of RA. Rheumatology (Oxford) 55 (2): 199–209.CrossRefPubMed
13.
Zurück zum Zitat Wang, J.M., W.D. Xu, Z.C. Yuan, Q. Wu, J. Zhou, and A.F. Huang. 2021. Serum levels and gene polymorphisms of angiopoietin 2 in systemic lupus erythematosus patients. Science and Reports 11 (1): 10.CrossRef Wang, J.M., W.D. Xu, Z.C. Yuan, Q. Wu, J. Zhou, and A.F. Huang. 2021. Serum levels and gene polymorphisms of angiopoietin 2 in systemic lupus erythematosus patients. Science and Reports 11 (1): 10.CrossRef
14.
Zurück zum Zitat Dai, C., S.J. Kuo, J. Zhao, L. Jin, L. Kang, L. Wang, et al. 2019. Correlation between genetic polymorphism of angiopoietin-2 gene and clinical aspects of rheumatoid arthritis. International Journal of Medical Sciences 16 (2): 331–336.CrossRefPubMedPubMedCentral Dai, C., S.J. Kuo, J. Zhao, L. Jin, L. Kang, L. Wang, et al. 2019. Correlation between genetic polymorphism of angiopoietin-2 gene and clinical aspects of rheumatoid arthritis. International Journal of Medical Sciences 16 (2): 331–336.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Hu, W., C.H. Tang, H.T. Chen, J. Zhao, L. Jin, L. Kang, et al. 2019. Correlations between angiopoietin-2 gene polymorphisms and lung cancer progression in a Chinese Han population. Journal of Cancer 10 (13): 2935–2941.CrossRefPubMedPubMedCentral Hu, W., C.H. Tang, H.T. Chen, J. Zhao, L. Jin, L. Kang, et al. 2019. Correlations between angiopoietin-2 gene polymorphisms and lung cancer progression in a Chinese Han population. Journal of Cancer 10 (13): 2935–2941.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Szederjesi, J., A. Lazar, M. Petrisor, A. Hutanu, F. Tripon, A.M. Georgescu, et al. 2020. Genetic variability of ANG2-35G>C gene as a predictor factor in sepsis. Revista Romana de Medicina de Laborator 28 (2): 175–184.CrossRef Szederjesi, J., A. Lazar, M. Petrisor, A. Hutanu, F. Tripon, A.M. Georgescu, et al. 2020. Genetic variability of ANG2-35G>C gene as a predictor factor in sepsis. Revista Romana de Medicina de Laborator 28 (2): 175–184.CrossRef
17.
Zurück zum Zitat Michalska-Jakubus, M., M. Rusek, M. Kowal, and D. Krasowska. 2021. Preliminary observations on ANGPT1 and ANGPT2 polymorphisms in systemic sclerosis: ANGPT2 rs2442598 and rs3739390 are associated with disease susceptibility and diffuse disease subtype. Polish Archives of Internal Medicine 131 (12): 16121.PubMed Michalska-Jakubus, M., M. Rusek, M. Kowal, and D. Krasowska. 2021. Preliminary observations on ANGPT1 and ANGPT2 polymorphisms in systemic sclerosis: ANGPT2 rs2442598 and rs3739390 are associated with disease susceptibility and diffuse disease subtype. Polish Archives of Internal Medicine 131 (12): 16121.PubMed
18.
Zurück zum Zitat Bhatraju, P.K., M. Cohen, R.J. Nagao, E.D. Morrell, S. Kosamo, X.Y. Chai, et al. 2020. Genetic variation implicates plasma angiopoietin-2 in the development of acute kidney injury sub-phenotypes. BMC Nephrology 21 (1): 284.CrossRefPubMedPubMedCentral Bhatraju, P.K., M. Cohen, R.J. Nagao, E.D. Morrell, S. Kosamo, X.Y. Chai, et al. 2020. Genetic variation implicates plasma angiopoietin-2 in the development of acute kidney injury sub-phenotypes. BMC Nephrology 21 (1): 284.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Omar, H., A.T. Abdellah, H. Abdalla, S.I. Nasef, and H. Omar. 2016. Angiopoietin-2 as A biomarker for echocardiographic abnormalities and carotid atherosclerosis in rheumatoid arthritis patients. The Egyptian Journal of Immunology 23 (2): 97–108.PubMed Omar, H., A.T. Abdellah, H. Abdalla, S.I. Nasef, and H. Omar. 2016. Angiopoietin-2 as A biomarker for echocardiographic abnormalities and carotid atherosclerosis in rheumatoid arthritis patients. The Egyptian Journal of Immunology 23 (2): 97–108.PubMed
20.
Zurück zum Zitat López-Mejías, R., A. Corrales, F. Genre, J.L. Hernández, R. Ochoa, R. Blanco, et al. 2013. Angiopoietin-2 serum levels correlate with severity, early onset and cardiovascular disease in patients with rheumatoid arthritis. Clinical & Experimental Rheumatology 31 (5): 761–766. López-Mejías, R., A. Corrales, F. Genre, J.L. Hernández, R. Ochoa, R. Blanco, et al. 2013. Angiopoietin-2 serum levels correlate with severity, early onset and cardiovascular disease in patients with rheumatoid arthritis. Clinical & Experimental Rheumatology 31 (5): 761–766.
21.
Zurück zum Zitat Omar, H.H., S.I. Nasef, and M.M. Anani. 2022. The association of angiopoietin-2 1064 C/T Rs3020221 gene polymorphism with knee osteoarthritis. Immunological Investigations 51 (6): 1820–1832.CrossRefPubMed Omar, H.H., S.I. Nasef, and M.M. Anani. 2022. The association of angiopoietin-2 1064 C/T Rs3020221 gene polymorphism with knee osteoarthritis. Immunological Investigations 51 (6): 1820–1832.CrossRefPubMed
22.
Zurück zum Zitat Aletaha, D., T. Neogi, A.J. Silman, J. Funovits, D.T. Felson, C.O. Bingham 3rd., et al. 2010. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis and Rheumatism 62 (9): 2569–2581.CrossRefPubMed Aletaha, D., T. Neogi, A.J. Silman, J. Funovits, D.T. Felson, C.O. Bingham 3rd., et al. 2010. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis and Rheumatism 62 (9): 2569–2581.CrossRefPubMed
24.
Zurück zum Zitat Anderson, J., L. Caplan, J. Yazdany, M.L. Robbins, T. Neogi, K. Michaud, et al. 2012. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care & Research 64 (5): 640–647.CrossRef Anderson, J., L. Caplan, J. Yazdany, M.L. Robbins, T. Neogi, K. Michaud, et al. 2012. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care & Research 64 (5): 640–647.CrossRef
25.
Zurück zum Zitat Akwii, R.G., M.S. Sajib, F.T. Zahra, and C.M. Mikelis. 2019. Role of angiopoietin-2 in vascular physiology and pathophysiology. Cells 8 (5): 471.CrossRefPubMedPubMedCentral Akwii, R.G., M.S. Sajib, F.T. Zahra, and C.M. Mikelis. 2019. Role of angiopoietin-2 in vascular physiology and pathophysiology. Cells 8 (5): 471.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Butkiewicz, D., A. Gdowicz-Kłosok, M. Krześniak, T. Rutkowski, A. Krzywon, A.J. Cortez, et al. 2020. Association of genetic variants in ANGPT/TEK and VEGF/VEGFR with progression and survival in head and neck squamous cell carcinoma treated with radiotherapy or radiochemotherapy. Cancers 12 (6): 1506.CrossRefPubMedPubMedCentral Butkiewicz, D., A. Gdowicz-Kłosok, M. Krześniak, T. Rutkowski, A. Krzywon, A.J. Cortez, et al. 2020. Association of genetic variants in ANGPT/TEK and VEGF/VEGFR with progression and survival in head and neck squamous cell carcinoma treated with radiotherapy or radiochemotherapy. Cancers 12 (6): 1506.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Marisi, G., E. Petracci, F. Raimondi, L. Faloppi, F.G. Foschi, G. Lauletta, et al. 2019. ANGPT2 and NOS3 polymorphisms and clinical outcome in advanced hepatocellular carcinoma patients receiving sorafenib. Cancers 11 (7): 1023.CrossRefPubMedPubMedCentral Marisi, G., E. Petracci, F. Raimondi, L. Faloppi, F.G. Foschi, G. Lauletta, et al. 2019. ANGPT2 and NOS3 polymorphisms and clinical outcome in advanced hepatocellular carcinoma patients receiving sorafenib. Cancers 11 (7): 1023.CrossRefPubMedPubMedCentral
Metadaten
Titel
Assessment of Angiopoietin-2 Single Nucleotide Polymorphism in Patients with Rheumatoid Arthritis
verfasst von
Samah Ismail Nasef
Alia Ellawindy
Aya Mohamed Askar
Asmaa AbdelKreem Hashem
Hanan Hassan Omar
Publikationsdatum
23.12.2022
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 3/2023
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-022-01773-3

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