Role of the IFNG +874T/A polymorphism in Chagas disease in a Colombian population

Abstract

Genetic susceptibility to Trypanosoma cruzi infection and the development of cardiomyopathy is complex, heterogeneous, and likely involves several genes. Previous studies have implicated cytokine and chemokine genes in susceptibility to Chagas disease. Here we investigated the association between the interferon-gamma gene (IFNG) +874T/A polymorphism and Chagas disease, focusing on susceptibility and severity. This study included 236 chagasic patients (asymptomatic, n=116; cardiomyopathic, n=120) and 282 healthy controls from a Colombian population where T. cruzi is highly endemic. Individuals were genotyped for functional single nucleotide polymorphism (SNP; rs2430561; A/T) of the IFNG gene by amplification refractory mutational system PCR (ARMS-PCR). Moreover, clinical manifestations of Chagas in patients were analyzed. We found a significant difference in the distribution of the IFNG +874 "A" allele between patients and healthy controls (P=0.003; OR=1.46, 95% CI, 1.13-1.89). The frequency of the IFNG +874 genotype A/A, which is associated with reduced production of interferon-gamma, was increased in the patients relative to controls (38.1% vs. 26.6%). We compared the frequencies of IFNG alleles and genotypes between asymptomatic patients and those with chagasic cardiomyopathy and found no significant difference. Our data suggest that the IFNG +874T/A genetic polymorphism may be involved in susceptibility but not in the progression of Chagas disease in this Colombian population.

Infection With Trypanosoma cruzi and Progression to Cardiomyopathy

“…The balance between proinflammatory and antiinflammatory cytokines may be critical in the chronic phase of the disease. [17][18][19][20] Studies on the specific role of cytokines in the immune response against T cruzi indicate that large amounts of both Th1 and proinflammatory cytokines such as interferon-γ and tumor necrosis factor-α are related to cardiac disease. [18][19][20] It is also known that these cytokines are regulated by antiinflammatory cytokines such…”

“…21,22 Recent studies indicate that the interferon-γ +874T/A genetic polymorphism may be involved in the susceptibility to but not in the progression of Chagas cardiomyopathy, linking inflammatory regulatory genes to the susceptibility to T cruzi infection. 17,18 Finally, autoantibodies directed to β 1 -and β 2 -adrenoreceptors and muscarinic-2 receptors have been documented in asymptomatic carriers and have been used to predict progression to cardiomyopathy, but larger studies are needed to validate these markers. 23 What is our current knowledge of the progression of Chagas disease in asymptomatic seropositive blood donors?…”

Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several genes of the innate immunity and chemokine-dependent migration pathways

“…Several genes were associated to an increased risk to develop cardiomyopathy (HLA, MHC, TNF, IL1A, IL1B, IL1RN, IL10, IL12B, TIRAP, CCL2, BAT1, LTA, IKBL, CCR5, MIF, IFNG, CXCL9, CXCL10) [25-50]. So far, up to 30 case control studies were done (see for review [51-53]).…”

Genetic Susceptibility to Chagas Disease: An Overview about the Infection and about the Association between Disease and the Immune Response Genes

“…Linkage disequilibrium analysis on microsatellite loci suggests epistasis between MHC and IL-10 on Chagas disease susceptibility/resistance [121]. The frequency of the IFNG+874AA (rs62559044), which is associated with reduced production of INF- γ , was increased in the Colombian patients suggesting that this SNP may be involved in susceptibility but not in the progression of Chagas disease [122]. …”