Interleukin 4, interleukin 4 receptor‐α and interleukin 10 gene polymorphisms in Chagas disease

Abstract

In this study, we investigated the association between single-nucleotide polymorphisms (SNPs) of the interleukin-4 (IL4), interleukin-4 receptor-α (IL4RA) and interleukin-10 (IL10) genes with the development of chagasic heart disease. This study included 260 patients from Colombia who were serologically positive for Trypanosoma cruzi antigens (cardiomyopathic, n=130; asymptomatic, n=130). Genotypes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism or sequence-specific primer methods. We found statistically significant differences in the distribution of the IL4RA +148 AA (P=0·025, OR=1·89, CI=1·04-3·43) genotype when comparing asymptomatic and symptomatic patients. No statistically significant differences in the genotype and allele frequency of IL4 and IL10 gene polymorphisms between symptomatic and asymptomatic patients were observed. Our experimental evidence suggests that the IL4RA +148 AA genotype has a weak association with the development of chagasic cardiomyopathy in the population under study.

Chagas Disease Cardiomyopathy: Immunopathology and Genetics

“…This was reported for the TLR1, TLR2, TLR4, TLR5, TLR9 [88], PTPN22 [89], NRAMP1 [90], ACE [91], NOS2 [92], CCL4, CCL5, CCL17, CCL19, and CXCR3 [41], beta-cardiac myosin heavy chain [58], IL4 [93], and IFNG [94]. Such lack of association or fault positive association may be due either to the limited number of tested SNPs or to the low statistical power owing to limited cohort size.…”

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

“…The SNP IL10-1082 (rs1800896) A allele, which is associated with a lower expression of IL-10, had higher frequency in CCC Brazilian patients when compared to the asymptomatic group [119]. However, in Colombian patients no differences in allele frequency and haplotype of the IL10 gene were observed in symptomatic and asymptomatic patients [120]. Linkage disequilibrium analysis on microsatellite loci suggests epistasis between MHC and IL-10 on Chagas disease susceptibility/resistance [121].…”

“…It can modulate the host and parasite survivals that depend on a fine balance between Th1 responses: on one hand it will control parasitism and, on the other hand, enhance heart inflammation throughout the course of the infection [123]. In a Bolivian population, SNP IL4-590 (rs2243250) T allele was associated with protection against T. cruzi infection [124], although in another study only the IL4RA (IL-4 receptor- α ; rs147781) +148AA genotype showed a weak association with the development of CCC [120]. …”

Chagas Heart Disease

“…Different groups have found markers associated with decreased production of anti-inflammatory cytokines in patients with CC (Costa et al, 2009). We have analyzed other genes of regulatory proteins, such as TGFB1 (Calzada et al, 2009), MIF (Torres et al, 2009), IL4, IL4RA and IL10 (Florez et al, 2011) which are associatted with CC. However, in the latter gene we were unable to demonstrate association between IL10 gene polymorphism and CD.…”