Functional IL18 polymorphism and susceptibility to Chronic Chagas Disease.
BACKGROUND
Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the rest of the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described. IL-18 could potentially amplify the process by inducing increased expression of IFN-γ which in turn can increase the production of IL-18, thereby creating a positive feedback mechanism. In order to assess the contribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the association between a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developing Chagas cardiomyopathy.


RESULTS
We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas disease cardiomyopathy patients (n=849) and asymptomatic subjects (n=202). We found a significant difference in genotype frequencies among moderate and severe CCC patients with ventricular dysfunction.


CONCLUSIONS
Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkage disequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome.
Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil. Electronic address: luciananogueira@usp.br.
Luciana Gabriel
LG
Nogueira
Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil. Electronic address: affrade@yahoo.com.br.
Amanda Farage
AF
Frade
Myocardiopathies Unit, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: barbara.ianni@incor.usp.br.
Barbara Maria
BM
Ianni
Aix-Marseille Université, INSERM, GIMP UMR_S906, 13385 Marseille, France. Electronic address: laugier.laurie@yahoo.fr.
Laurie
L
Laugier
Laboratory of Immunology, Universidade Federal do Triângulo Mineiro (UFTM), 40 Frei Paulino, 48036-180 Uberaba, MG, Brazil. Electronic address: cristinawpissetti@gmail.com.
Cristina Wide
CW
Pissetti
Aix-Marseille Université, INSERM, GIMP UMR_S906, 13385 Marseille, France. Electronic address: sandrine.ambard@univ-amu.fr.
Sandrine
S
Cabantous
Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil. Electronic address: moni.baron@hotmail.com.
Monique
M
Baron
Pacemaker Clinic, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: gisellepeixoto@ig.com.br.
Gisele de Lima
Gde L
Peixoto
Laboratory of Immunology, Universidade Federal do Triângulo Mineiro (UFTM), 40 Frei Paulino, 48036-180 Uberaba, MG, Brazil. Electronic address: ariana_borges@hotmail.com.
Ariana de Melo
Ade M
Borges
School of Medicine of Ribeirão Preto (FMRP), University of São Paulo, São Paulo, Brazil. Electronic address: eadonadi@fmrp.usp.br.
Eduardo
E
Donadi
School of Medicine of Ribeirão Preto (FMRP), University of São Paulo, São Paulo, Brazil. Electronic address: jamneto@fmrp.usp.br.
José A
JA
Marin-Neto
School of Medicine of Ribeirão Preto (FMRP), University of São Paulo, São Paulo, Brazil. Electronic address: aschmidt@fmrp.usp.br.
André
A
Schmidt
School of Medicine of Ribeirão Preto (FMRP), University of São Paulo, São Paulo, Brazil. Electronic address: diasfc@gmail.com.
Fabrício
F
Dias
Dante Pazzanese Institute of Cardiology and Heart Failure Unit, São Paulo, Brazil. Electronic address: brunosaba@hotmail.com.
Bruno
B
Saba
Dante Pazzanese Institute of Cardiology and Heart Failure Unit, São Paulo, Brazil. Electronic address: lin.ht.wang@gmail.com.
Hui-Tzu Lin
HT
Wang
Dante Pazzanese Institute of Cardiology and Heart Failure Unit, São Paulo, Brazil. Electronic address: a.frag@terra.com.br.
Abilio
A
Fragata
Dante Pazzanese Institute of Cardiology and Heart Failure Unit, São Paulo, Brazil. Electronic address: msampaio@cardiol.br.
Marcelo
M
Sampaio
Dante Pazzanese Institute of Cardiology and Heart Failure Unit, São Paulo, Brazil. Electronic address: mhhirata@usp.br.
Mario Hiroyuki
MH
Hirata
Myocardiopathies Unit, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: paula.buck@uol.com.br.
Paula
P
Buck
Myocardiopathies Unit, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: charles.mady@incor.usp.br.
Charles
C
Mady
Pacemaker Clinic, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: martino.filho@incor.usp.br.
Martino
M
Martinelli
Pacemaker Clinic, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: marilensi@hotmail.com.
Mariana
M
Lensi
Pacemaker Clinic, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: siqueira@incor.usp.br.
Sergio Freitas
SF
Siqueira
Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: alexandre.pereira@incor.usp.br.
Alexandre Costa
AC
Pereira
Laboratory of Immunology, Universidade Federal do Triângulo Mineiro (UFTM), 40 Frei Paulino, 48036-180 Uberaba, MG, Brazil. Electronic address: vrodrigues@mednet.com.br.
Virmondes
V
Rodrigues
Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil. Electronic address: jkalil@usp.br.
Jorge
J
Kalil
Aix-Marseille Université, INSERM, GIMP UMR_S906, 13385 Marseille, France. Electronic address: christophe.chevillard@univ-amu.fr.
Christophe
C
Chevillard
Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil. Electronic address: edecunha@gmail.com.
Edecio
E
Cunha-Neto
D016022:Case-Control Studies; D002598:Chagas Cardiomyopathy / Q000235:genetics* / Q000503:physiopathology; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013318:Stroke Volume
D020382:Interleukin-18
Cardiomyopathy; Chagas; IL18; Severity; polymorphism