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

被引:31
作者
Fernández-Mestre, MT [1 ]
Montagnani, S [1 ]
Layrisse, Z [1 ]
机构
[1] Inst Venezolano Invest Cient, Lab Fisiopatol, Ctr Med Expt Miguel Layrisse, Caracas 1020, Venezuela
关键词
Chagas disease; CCR5; polymorphism; Trypanosoma cruzi;
D O I
10.1016/j.humimm.2004.05.002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Investigated were two CCR5 gene polymorphisms, the CCR5Delta32 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 CCR5Delta32 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.
引用
收藏
页码:725 / 728
页数:4
相关论文
共 22 条
[1]  
Abdi R, 2002, J AM SOC NEPHROL, V13, DOI 10.1681/ASN.V133754
[2]   LONG-TERM CONTROL OF CHAGAS-DISEASE IN VENEZUELA - EFFECTS ON SEROLOGIC FINDINGS, ELECTROCARDIOGRAPHIC ABNORMALITIES, AND CLINICAL OUTCOME [J].
ACQUATELLA, H ;
CATALIOTI, F ;
GOMEZMANCEBO, JR ;
DAVALOS, V ;
VILLALOBOS, L .
CIRCULATION, 1987, 76 (03) :556-562
[3]   β-chemokines enhance parasite uptake and promote nitric oxide-dependent microbiostatic activity in murine inflammatory macrophages infected with Trypanosoma cruzi [J].
Aliberti, JCS ;
Machado, FS ;
Souto, JT ;
Campanelli, AP ;
Teixeira, MM ;
Gazzinelli, RT ;
Silva, JS .
INFECTION AND IMMUNITY, 1999, 67 (09) :4819-4826
[4]   Influence of CCR5 promoter haplotypes on AIDS progression in African-Americans [J].
An, P ;
Martin, MP ;
Nelson, GW ;
Carrington, M ;
Smith, MW ;
Gong, K ;
Vlahov, D ;
O'Brien, SJ ;
Winkler, CA .
AIDS, 2000, 14 (14) :2117-2122
[5]   Chemokine receptor CCR5 polymorphisms and Chagas' disease cardiomyopathy [J].
Calzada, JE ;
Nieto, A ;
Beraún, Y ;
Martín, J .
TISSUE ANTIGENS, 2001, 58 (03) :154-158
[6]  
FLEISS JL, 1979, STAT METHODS RATES P
[7]  
Guignard F, 1998, J IMMUNOL, V160, P985
[8]  
HALDANE JBS, 1956, ANN HUM GENET, V20, P309
[9]   The role of a mutant CCR5 allele in HIV-1 transmission and disease progression [J].
Huang, YX ;
Paxton, WA ;
Wolinsky, SM ;
Neumann, AU ;
Zhang, LQ ;
He, T ;
Kang, S ;
Ceradini, D ;
Jin, ZQ ;
Yazdanbakhsh, K ;
Kunstman, K ;
Erickson, D ;
Dragon, E ;
Landau, NR ;
Phair, J ;
Ho, DD ;
Koup, RA .
NATURE MEDICINE, 1996, 2 (11) :1240-1243
[10]   Trypanosoma cruzi-elicited CD8+ T cell-mediated myocarditis:: Chemokine receptors and adhesion molecules as potential therapeutic targets to control chronic inflammation? [J].
Lannes-Vieira, J .
MEMORIAS DO INSTITUTO OSWALDO CRUZ, 2003, 98 (03) :299-304