Novel Polymorphism in a Promoter of MBL2 Gene Result in Lower MBL Expression in Chronic Infection Caused by HCV
https://doi.org/10.24017/science.2020.ICHMS2020.13
Abstract views: 1217 / PDF downloads: 649Abstract
The Pathogen Recognition Receptors (PRRs) is an active protein in the immune system. The PRRs that secreted in the liver and we addressed were L-ficolin, MBL and H-ficolin. Previous studies revealed that both MBL and L-ficolin were hampered the HCV entry and infectivity. However, H-ficolin impact still needs to be addressed more so as determining their role during HCV infection. For these purposes, we aimed to determine the effect of different level in the serum of these proteins on the HCV infection and treatment outcome. Initially, we selected (25) HCV positive patients and (25) HCV negative control patients from the Trent Cohort and Regional Haemophiliac Study and to present the differences in serum concentrations of MBL, H- and L-ficolin. The level of these proteins was measured by ELISA method and compared with each other based on the detected SNPs by PCR and sequencing methods in the responsible genes. Our results showed that the polymorphism at position -221 in the MBL2 promoter significantly reduce the level of MBL protein more than the SNP at position -551. Interestingly, a new deletion of six nucleotides [AGGAAG] detected in the promoter at position -319 to -324 that succeeded by four other mutations at position -328, -336, -349 and -427 in most of the analyzed sequences. The 6bp deletion was statistically decreasing the concentration of MBL below 1µg.mL-1, precisely among non-responder patients. In conclusion, the existence of the new deletion in the promoter region of MBL2 gene and the additional newly detected polymorphisms, reduce the level of MBL protein and as a result impacts on the response to treatment among HCV-infected patients.
Keywords:
MBL, SNPs, PRRs, L-ficolin, H-ficolin, HCV infection.
References
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https://doi.org/10.1111/j.1365-2249.2006.03264.x
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https://doi.org/10.1016/j.molimm.2007.06.005
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https://doi.org/10.1159/000362209
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https://doi.org/10.1111/j.1399-0039.2006.00649.x
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https://doi.org/10.1016/j.molimm.2007.10.006
[12] T. Fujita, M. Matsushita, and Y. Endo, "The lectin-complement pathway - its role in innate immunity and evolution," Immunological Reviews, vol. 198, pp. 185-202, 2004.
https://doi.org/10.1111/j.0105-2896.2004.0123.x
[13] V. Garlatti, L. Martin, M. Lacroix, E. Gout, G. J. Arlaud, N. M. Thielens, et al., "Structural insights into the recognition properties of human ficolins," J Innate Immun, vol. 2, pp. 17-23, 2010.
https://doi.org/10.1159/000233475
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https://doi.org/10.1034/j.1600-065X.2001.1800108.x
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https://doi.org/10.2147/CMAR.S28688
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https://doi.org/10.1111/j.1365-2249.1997.tb08334.x
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https://doi.org/10.1016/0140-6736(91)93263-9
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https://doi.org/10.1016/S0140-6736(95)90009-8
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https://doi.org/10.1128/JVI.79.14.9192-9196.2005
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https://doi.org/10.4049/jimmunol.155.6.3013
[21] S. Pfaender, J. Brinkmann, D. Todt, N. Riebesehl, J. Steinmann, J. Steinmann, et al., "Mechanisms of methods for hepatitis C virus inactivation," Appl Environ Microbiol, vol. 81, pp. 1616-21, Mar 2015.
https://doi.org/10.1128/AEM.03580-14
[22] K. S. Brown, S. D. Ryder, W. L. Irving, R. B. Sim, and T. P. Hickling, "Mannan binding lectin and viral hepatitis," Immunol Lett, vol. 108, pp. 34-44, Jan 15 2007.
https://doi.org/10.1016/j.imlet.2006.10.006
[23] A. Krarup, S. Thiel, A. Hansen, T. Fujita, and J. C. Jensenius, "L-ficolin Is a Pattern Recognition Molecule Specific for Acetyl Groups," THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 279 pp. 47513-47519, 2004.
https://doi.org/10.1074/jbc.M407161200
[24] M. Scorza, R. Liguori, A. Elce, F. Salvatore, and G. Castaldo, "Biological role of mannose binding lectin: From newborns to centenarians," Clin Chim Acta, vol. 451, pp. 78-81, Dec 7 2015.
https://doi.org/10.1016/j.cca.2015.03.007
[25] I. Terai and K. Kobayashi, "Perinatal changes in serum mannose-binding protein (MBP) levels," Immunol Lett, vol. 38, pp. 185-7, Nov 1993.
https://doi.org/10.1016/0165-2478(93)90004-L
[26] A. M. Oudshoorn, F. A. van den Dungen, K. P. Bach, I. Koomen, W. P. Fetter, A. Catsburg, et al., "Mannose-binding lectin in term newborns and their mothers: genotypic and phenotypic relationship," Hum Immunol, vol. 69, pp. 344-8, Jun 2008.
https://doi.org/10.1016/j.humimm.2008.04.010
[27] E. E. Brown, M. Zhang, R. Zarin-Pass, T. Bernig, F.-C. Tseng, N. Xiao, et al., "MBL2 and Hepatitis C Virus Infection among Injection Drug Users," BMC Infectious Diseases vol. 8, 2008.
https://doi.org/10.1186/1471-2334-8-57
[28] P. Garred, F. Larsen, H. O. Madsena, and C. Koch, "Mannose-binding lectin deficiency-revisited," Molecular Immunology, vol. 40, pp. 73-84, 2003.
https://doi.org/10.1016/S0161-5890(03)00104-4
[29] R. Steffensen, S. Thiel, K. Varming, C. Jersild, and J. C. Jensenius, "Detection of structural gene mutations and promoter polymorphisms in the mannan-binding lectin (MBL) gene by polymerase chain reaction with sequence-specific primers," Journal of Immunological Methods, vol. 241, pp. 33-42, 2000.
https://doi.org/10.1016/S0022-1759(00)00198-8
[30] P. Garred, S. Thiel, H. O. Madsen, L. P. Ryder, J. C. Jensenius, and A. Svejgaard, "Gene frequency and partial protein characterization of an allelic variant of mannan binding protein associated with low serum concentrations," Clin. exp. Immunol., vol. 90 pp. 517-521, 1992.
https://doi.org/10.1111/j.1365-2249.1992.tb05876.x
[31] M. Matsushita, M. Hijikata, Y. Ohta, K. Iwata, M. Matsumoto, K. Nakao, et al., "Hepatitis C virus infection and mutations of mannose-binding lectin gene MBL," Arch Virol, vol. 143, pp. 645-651, 1998.
https://doi.org/10.1007/s007050050320
[32] Y. Lin, C. Su, J. Niu, Z. Guo, and L. Cai, "Impact of mannose-binding lectin 2 polymorphism on the risk of hepatocellular carcinoma: a case-control study in Chinese Han population," J Epidemiol, vol. 25, pp. 387-91, 2015.
https://doi.org/10.2188/jea.JE20140194
[33] X. Gu, Q. Ji, H. Wang, M. Jiang, J. Yang, M. Fang, et al., "Genetic variants of mannose-binding lectin 2 gene influence progression and prognosis of patients with hepatitis B virus infection in China," Clin Res Hepatol Gastroenterol, Feb 5 2016.
https://doi.org/10.1016/j.clinre.2015.12.015
[34] J. Liu, M. A. M. Ali, Y. Shi, Y. Zhao, F. Luo, J. Yu, et al., "Specifically Binding of L-ficolin to N-glycans of HCV Envelope Glycoproteins E1 and E2 Leads to Complement Activation," Cellular & Molecular Immunology, vol. 6, pp. 235-244, 2009.
https://doi.org/10.1038/cmi.2009.32
[35] J. M. Pawlotsky, "Therapy of hepatitis C: from empiricism to eradication," Hepatology, vol. 43, pp. S207-20, Feb 2006.
https://doi.org/10.1002/hep.21064
[36] K. Sasaki, A. Tsutsumi, and N. Wakamiya, "Mannose-Binding Lectin Polymorphisms in Patients with Hepatitis C Virus Infection," Scandinavian Journal of Gastroenterology, vol. 35, pp. 960-965, 2009.
https://doi.org/10.1080/003655200750023039
[37] D. C. Kilpatrick, T. E. S. Delahooke, C. Koch, M. L. Turner, and P. C. Hayes, "Mannan-binding lectin and hepatitis C infection," Clin Exp Immunol vol. 132, pp. 92-95, 2003.
https://doi.org/10.1046/j.1365-2249.2003.02122.x
[38] A. C. Vallinoto, R. F. da Silva, R. B. Hermes, I. S. Amaral, E. C. Miranda, M. S. Barbosa, et al., "Mannose-binding lectin gene polymorphisms are not associated with susceptibility to hepatitis C virus infection in the Brazilian Amazon region," Hum Immunol, vol. 70, pp. 754-7, Sep 2009.
https://doi.org/10.1016/j.humimm.2009.06.014
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https://doi.org/10.1111/sji.12444
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P. Jamal Jalal, “Novel Polymorphism in a Promoter of MBL2 Gene Result in Lower MBL Expression in Chronic Infection Caused by HCV”, KJAR, vol. 6, no. 3, pp. 116–128, Dec. 2020, doi: 10.24017/science.2020.ICHMS2020.13.
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12-12-2020
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Pure and Applied Science
