Is the CCR5-59029-G/G genotype a protective factor for cardiomyopathy in Chagas disease?
Investigated were two CCR5 gene polymorphisms, the CCR5 Delta 32 deletion and the pCCR5 59029 A-->G promoter point mutation, in 107 ethnically mixed Venezuelan patients serologically positive for Trypanosoma cruzi (34 asymptomatic, 38 arrhythmic, 35 cardiomyopathic). No difference in the distribution of CCR5 Delta 32 among asymptomatic and symptomatic patients was found. We have observed an increase of the 59029-G phenotype among asymptomatic compared with symptomatic chagasic patients (68% vs. 58%), in agreement with previously reported data (57% vs. 31%). This frequency difference, although not statistically significant, is more marked when the 59029-G allele is present in homozygous form. However, a similar distribution of the G/G genotype is present among asymptomatic patients and patients with heart failure. Because it has been reported that the 59029G/G genotype associates with lower CCR5 expression, 37% of our T. cruzi-infected patients with heart failure are genetically predisposed to express low levels of CCR5 on the surface of CD8(+) T cells, contrary to what would be expected if an inflammatory response is required for severe cardiac damage. If confirmed, the possible protection that might be conferred by the G/G genotype may be due to the existence of other genes in linkage disequilibria.
Laboratorio de Fisiopatología, Instituto Venezolano de Investigaciones Científicas, Caracas 1020a, Venezuela.
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Fernández-Mestre
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Montagnani
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Layrisse
D000818:Animals; D002598:Chagas Cardiomyopathy / Q000175:diagnosis / Q000235:genetics*; D014355:Chagas Disease / Q000208:ethnology / Q000235:genetics* / Q000469:parasitology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004587:Electrophoresis, Agar Gel; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics*; D014349:Trypanosoma cruzi / Q000276:immunology; D014687:Venezuela
D019713:Receptors, CCR5; D004247:DNA