{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIn humans the mannose-binding lectin (MBL) genetic system comprises a functional gene (MBL2) and an expressed pseudogene (MBL1P1). The MBL1P1 gene, originally coding for a protein with collagen-like and carbohydrate recognition domains, has been repeatedly inactivated over evolution by mutations—particularly in its glycine-rich collagen-like region—resulting in its silencing. This evolutionary “turning off” mirrors the molecular events that generate structural and promoter polymorphisms in MBL2 and has been suggested to reflect selective pressures driving low MBL production in man."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMBL itself plays a central role in innate immune defense acting as a serum opsonin and initiating complement activation via the lectin pathway. Several studies have examined genetic polymorphisms in MBL with respect to various clinical conditions—from hepatitis B virus infection, where codon 54 variants do not significantly affect clearance or disease progression, to coronary artery reactivity, which represents early atherogenic changes, as well as susceptibility to tuberculosis and certain vasculitides. While these investigations focus primarily on polymorphic alterations in the functional MBL gene (MBL2), they underscore the overall importance of regulated MBL expression in mediating host-pathogen interactions and inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn summary, although MBL1P1 no longer encodes a functional protein, its evolutionary silencing provides important insight into the regulation of MBL expression. The inactivation of MBL1P1—via similar mutations that affect critical structural domains in MBL2 variants—illustrates a potential evolutionary strategy to moderate complement activation and inflammatory responses, thereby balancing the benefits and risks of MBL-mediated immunity.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jeanette Seyfarth, Peter Garred, Hans O Madsen "}, {"type": "b", "children": [{"type": "t", "text": "The 'involution' of mannose-binding lectin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddi318"}], "href": "https://doi.org/10.1093/hmg/ddi318"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16115813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16115813"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jae Youn Cheong, Sung Won Cho, Sun Kyo Lim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lack of association between hepatitis B virus infection and polymorphism of mannose-binding lectin gene in Korean population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Korean Med Sci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3346/jkms.2005.20.1.65"}], "href": "https://doi.org/10.3346/jkms.2005.20.1.65"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15716605"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15716605"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Janne Aittoniemi, Yue-Mei Fan, Reijo Laaksonen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The effect of mannan-binding lectin variant alleles on coronary artery reactivity in healthy young men."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cardiol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ijcard.2003.06.027"}], "href": "https://doi.org/10.1016/j.ijcard.2003.06.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15458704"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15458704"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Huey-Ling You, Tsun-Mei Lin, Jui-Chu Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mannose-binding lectin gene polymorphisms and mycobacterial lymphadenitis in young patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Infect Dis J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/INF.0b013e31829e6798"}], "href": "https://doi.org/10.1097/INF.0b013e31829e6798"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24008740"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24008740"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Burak Durmaz, Ayca Aykut, Gultac Hursitoglu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of mannose binding lectin codon 54 polymorphism with predisposition to Henoch-Schönlein purpura in childhood."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Rheum Dis (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/1756-185X.12321"}], "href": "https://doi.org/10.1111/1756-185X.12321"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24576294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24576294"}]}]}]}