Association of L-Ficolin Levels and FCN2 Genotypes with Chronic Chagas Disease.docVIP

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Association of L-Ficolin Levels and FCN2 Genotypes with Chronic Chagas Disease.doc

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Association of L-Ficolin Levels and FCN2 Genotypes with Chronic Chagas Disease

AssociationofL-FicolinLevelsandFCN2Genotypeswith ChronicChagasDisease PaolaR.Luz1,AngelicaB.W.Boldt1,CarolineGrisbach1,Ju¨rgenF.J.Kun2,ThirumalaisamyP.Velavan2*., IaraJ.T.Messias-Reason1*. 1Laborato′rio de Imunopatologia Molecular – Departamento de Patologia Me′dica, Hospital de Cl?′nicas, Universidade Federal do Parana′, Curitiba, Brazil, 2Institute of TropicalMedicine,UniversityofTuebingen,Tuebingen,Germany Abstract Background:L-ficolin(encodedbyFCN2)bindstoacetylatedsugarmoietiesofmanypathogens,includingTrypanosoma cruzi,promotingtheirphagocytosisandlysisbythecomplementsystem. Methods: We investigated L-ficolin levels in 160 T. cruzi infected patients with chronic Chagas disease and 71 healthy individuals,andFCN2polymorphisms(2986G.A,2602G.A,and24A.GinthepromoterandA258Sinexon8)in243 patients, being 88 indeterminate (asymptomatic), 96 with cardiac, 23 with digestive and 33 with cardiodigestive manifestations(twowereunspecified)and305controls(135forA258S). Results:PatientspresentedlowerL-ficolinplasmalevelsthancontrols(p,0.0001).Amongthedifferentgroupsofcardiac commitment,individualswithmoderateformshadhigherL-ficolinlevelsthanthesevereforms(P=0.039).LowerL-ficolin levelswerefoundassociatedwiththe258Svariantinthepatients(P=0.034).Wefoundless24A/Gheterozygotesinthe cardiacpatients,thaninthecontrols(OR=0.56[95%CI=0.33–0.94],P=0.034).Heterozygote24A/Ggenotypeswiththe 258S variant and 258SS homozygotes were nevertheless more frequent among cardiodigestive patients than in controls (OR=14.1 [95% CI=3.5–56.8], P=0.0001) and in indeterminate patients (OR=3.2 [95% CI=1.1–9.4], P=0.037). We also foundanassociationoftheallelicfrequencyofthe258SvariantwithcardiodigestiveChagasdiseasecomparedtocontrols (OR=2.24[95%CI=1.1–4.5],P=0.037).Thus,decreasedpatientlevelsofL-ficolinreflectnotonlyproteinconsumptiondue tothediseaseprocess,butalsothehigherfrequencyofthe258Svariantinpatientswithcardiodigestivesymptoms. Conclusion: The very first study on Brazilian cohort associates both