%0 Journal Article
%T Genetically Determined MBL Deficiency Is Associated with Protection against Chronic Cardiomyopathy in Chagas Disease
%A Paola Rosa Luz&nbsp
%A M¨˘rcia I. Miyazaki&nbsp
%A Nelson Chiminacio Neto&nbsp
%A Marcela C. Padeski&nbsp
%A Ana Cl¨˘udia M. Barros&nbsp
%A Angelica B. W. Boldt&nbsp
%A Iara J. Messias-Reason
%J PLOS Neglected Tropical Diseases
%D 2016
%I Public Library of Science (PLoS)
%R 10.1371/journal.pntd.0004257
%X 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.
%U http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0004257