immunology of infectious and parasitic diseases - XXXVII Congress ...

Title: VPAC1 GENE POLYMORPHISM IS ASSOCIATED WITH THE
INDETERMINATE FORM OF CHAGAS DISEASE
MARIELLE VALERIO CORREA(PG)(1); MANOEL OTÁVIO DA COSTA
ROCHA(2); NATALIA SATCHIKO HOJO DE SOUSA(PG)(1); KARINE
SILVESTRE FERREIRA(PG)(1); KENNETH JOHN GOLLOB(3,4,6);
WALDEREZ ORNELAS DUTRA(1,3,6); CRISTIANE ALVES DA SILVA
MENEZES(5,6).
(1).Departamento de Morfologia da Universidade Federal de Minas Gerais;
(2).Faculdade de Medicina da Universidade Federal de Minas Gerais; (3).
Center for Infectious Disease Research, SRI International, Menlo Park, CA,
USA; (4). Instituto de Ensino e Pesquisa Programa de Pos-graduação em
Biomedicina e Medicina, Hospital Santa Casa BH; (5). Instituto de Ciências
Exatas e Biológicas da Universidade Federal de Ouro Preto; (6) INCT-DT.
Introduction: Human infection with T. cruzi leads to Chagas disease (CD),
which presents as several different clinical phenotypes ranging from an
asymptomatic form to a severe dilated cardiomyopathy. Host‟s immune system
plays a critical role in parasitemia control; however, exacerbated cellular
response can cause tissue damage. Interactions between the immune, nervous
and endocrine systems play an important role in modulating host susceptibility
and resistance to inflammatory and infectious diseases through the
homeostasis maintenance of cellular response. Vasoactive intestinal peptide
(VIP) is a neuropeptide with a broad distribution in the body and exerts a role as
a modulator of the homeostasis of the immune system through its receptors
VPAC1 and VPAC2. Data concerning to VIP or its receptors function in the
scenario of CD are lacking in literature. Considering this, and the variation in
clinical forms of CD, we hypothesized that an aberrant response to VIP could be
related to development of different clinical outcomes and associated to VPAC
polymorphisms. Thus, the present study aims to analyze if gene polymorphisms
of VIP receptors, may be associated with different clinical forms of CD.
Methods and Results: To assess possible associations between single
nucleotide polymorphisms of genes encoding VPAC1 and VPAC2 and the
development of CD, DNA was obtained from oral swabs of a cohort of 144
individuals (57 patients with dilated cardiomiopathy, 51 patients with
indeterminate form and 51 non infected individuals) and the evaluation of
polymorphisms are being performed using Real Time PCR. Statistical analysis
of data was performed using the chi(2) likelihood ratio test. The study groups
were tested for Hardy-Weinberg equilibrium comparing the expected with the
observed genotypes frequencies for VPAC1 SNP rs342511 (2234 C/T) (X 2
=0,0079; p=0,9292). Our data showed that patients carrying the T variant for
VPAC1 have four times more chance of developing the indeterminate form as
compared to the cardiac form (X 2 = 5, 179; OR= 4,267; p=0,023; IC=0,336-
2,976).