Genetically Determined MBL Deficiency Is Associated with Protection against Chronic Cardiomyopathy in Chagas Disease.
| Autor: | Paola Rosa Luz, Márcia I Miyazaki, Nelson Chiminacio Neto, Marcela C Padeski, Ana Cláudia M Barros, Angelica B W Boldt, Iara J Messias-Reason |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | PLoS Neglected Tropical Diseases, Vol 10, Iss 1, p e0004257 (2016) |
| Druh dokumentu: | article |
| ISSN: | 1935-2727 1935-2735 |
| DOI: | 10.1371/journal.pntd.0004257 |
| Popis: | Chagas disease (CD) is caused by Trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (MBL), a soluble pattern-recognition molecule that activates the lectin pathway of complement. MBL levels and protein activity are affected by polymorphisms in the MBL2 gene. We sequenced the MBL2 promoter and exon 1 in 196 chronic CD patients and 202 controls. The MBL2*C allele, which causes MBL deficiency, was associated with protection against CD (P = 0.007, OR = 0.32). Compared with controls, genotypes with this allele were completely absent in patients with the cardiac form of the disease (P = 0.003). Furthermore, cardiac patients with genotypes causing MBL deficiency presented less heart damage (P = 0.003, OR = 0.23), compared with cardiac patients having the XA haplotype causing low MBL levels, but fully capable of activating complement (P = 0.005, OR = 7.07). Among the patients, those with alleles causing MBL deficiency presented lower levels of cytokines and chemokines possibly implicated in symptom development (IL9, p = 0.013; PDGFB, p = 0.036 and RANTES, p = 0.031). These findings suggest a protective effect of genetically determined MBL deficiency against the development and progression of chronic CD cardiomyopathy. |
| Databáze: | Directory of Open Access Journals |
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