Is the CCR5-59029-G/G genotype a protective factor for cardiomyopathy in Chagas disease?

Type 1 Chemokine Receptor Expression in Chagas' Disease Correlates with Morbidity in Cardiac Patients

“…2 and 3 and Table 1). These data are consistent with recent findings in Peruvian T. cruzi-seropositive patients, demonstrating the higher frequency of the CCR5 promoter point mutation (CCR5 59029 A G) in asymptomatic individuals in comparison with CARD patients (7,13) and provide a genetic explanation for the differential expression of this chemokine receptor between the two groups of T. cruzi-infected individuals, with or without cardiac disease. The authors of these suggest that the presence of this point mutation duet 59029-G may result in reduced expression of CCR5 on the cells membrane of individuals bearing this allele.…”

“…The explanation of Talvani et al for this fact, in the context of chagasic pathology, diverges from that presented here and discussed by Calzada and coworkers (7,13). The information on the cytokine production profile by CCR5 ϩ T cells provided in this study (not approached in the Talvani study) support the interpretation of the Calzada group that the mutated CCR5 genotype protects T. cruzi-seropositive individuals from developing chagasic cardiomyopathy.…”

Genetic variants in the chemokines and chemokine receptors in Chagas disease

“…Previous studies have established the association of CCR5À2459 G allele and GG genotype with the differential susceptibility to CD in Peruvian and Venezuelan populations, which suggest this polymorphism is a protective factor [16,17]. The transcriptional regulatory activity of CCR5À2459 A allele produces a higher gene expression than that of CCR5À2459 G allele [42,43].…”

“…However, genetic susceptibility to T. cruzi infection and the development of cardiomyopathy is complex and heterogeneous and likely involves several genes, each with a modest contribution on the pathogenesis of the disease. In fact, genetic studies in human beings have addressed the relation between cytokine and chemokine gene polymorphisms and development of chagasic heart disease [16][17][18][19][20][21][22]. In this study, we investigated the possible association of CCL5/RANTES and CXCL8/interleukin 8 (IL-8) chemokines, and CCR2 and CCR5 chemokines receptors cluster gene polymorphisms with the development of chagasic cardiomyopathy in a case-control study in Colombia endemic area.…”

CC-chemokine receptors: a potential therapeutic target for Trypanosoma cruzi-elicited myocarditis

“…The expression of CCR5 (receptor for CCL5/ RANTES, CCL3/MIP-1α and CCL4/MIP-1β) alleles was analyzed in chagasic patients. Interestingly, two independent studies have shown that the CCR5-59029G allele, associated with CCR5 low expression, is more frequent in asymptomatic as compared with cardiomyophatic T. cruzi-infected patients (Calzada et al 2001, Fernandez-Mestre et al 2004. These results indicate a role for this chemokine receptor in the pathogenesis of chagasic cardiomyopathy.…”