title: Genetically Determined MBL Deficiency Is Associated with Protection against Chronic Cardiomyopathy in Chagas Disease.
abstract: 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.
authors.affiliation: Laboratório de Imunopatologia Molecular-Departamento de Patologia Médica, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brasil.
authors.forename: Paola Rosa
authors.initials: PR
authors.lastname: Luz
authors.affiliation: Ambulatório de Atenção ao Paciente Chagásico-Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brasil.
authors.forename: Márcia I
authors.initials: MI
authors.lastname: Miyazaki
authors.affiliation: Serviço de Ecocardiografia-Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brasil.
authors.forename: Nelson
authors.initials: N
authors.lastname: Chiminacio Neto
authors.affiliation: Laboratório de Imunopatologia Molecular-Departamento de Patologia Médica, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brasil.
authors.forename: Marcela C
authors.initials: MC
authors.lastname: Padeski
authors.affiliation: Laboratório de Imunopatologia Molecular-Departamento de Patologia Médica, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brasil.
authors.forename: Ana Cláudia M
authors.initials: AC
authors.lastname: Barros
authors.affiliation: Laboratório de Imunopatologia Molecular-Departamento de Patologia Médica, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brasil.|Laboratório de Genética Molecular Humana-Departamento de Genética, Universidade Federal do Paraná, Curitiba, Brasil.
authors.forename: Angelica B W
authors.initials: AB
authors.lastname: Boldt
authors.affiliation: Laboratório de Imunopatologia Molecular-Departamento de Patologia Médica, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brasil.
authors.forename: Iara J
authors.initials: IJ
authors.lastname: Messias-Reason
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002598:Chagas Cardiomyopathy / Q000235:genetics* / Q000517:prevention & control*; D060467:Disease Resistance; D005260:Female; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency* / Q000235:genetics; D008661:Metabolism, Inborn Errors; D008875:Middle Aged; D055815:Young Adult
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin