The monocyte chemoattractant protein-1 gene polymorphism is associated with cardiomyopathy in human chagas disease
| Autor: | Anna Carla Goldberg, Fernanda G. Martello, Vanessa L. Cavalcanti, Charles Mady, Kellen C. Faé, Edecio Cunha-Neto, Natalie Guida Muller, Barbara Maria Ianni, Jorge Kalil, Rajendranath Ramasawmy |
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| Rok vydání: | 2006 |
| Předmět: |
Microbiology (medical)
Chagas disease Chagas Cardiomyopathy Male Genotype Biology Asymptomatic Gene Frequency medicine Humans Genetic Predisposition to Disease Allele Trypanosoma cruzi Allele frequency Chemokine CCL2 Aged Polymorphism Genetic Heterozygote advantage Middle Aged biology.organism_classification medicine.disease Infectious Diseases Immunology Female Gene polymorphism medicine.symptom |
| Zdroj: | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 43(3) |
| ISSN: | 1537-6591 |
| Popis: | Background Only a subset of individuals infected with Trypanosoma cruzi develop chronic Chagas cardiomyopathy (CCC). Familial aggregation of CCC in areas of endemicity indicates that susceptibility may be genetic, which may be a plausible explanation for why only one-third of T. cruzi-infected individuals develop CCC. The monocyte chemoattractant protein-1 (CCL2/MCP-1) has been shown to enhance the uptake of T. cruzi in murine macrophages and to up-regulate the inducible nitric oxide synthase/nitric oxide system, with a consequent increased production of nitric oxide that controls the replication of the parasite. Methods We assessed CCL2 variants at position -2518A/G, which are known to influence transcriptional activity, by polymerase chain reaction and restriction fragment-length polymorphism in 245 individuals, all of whom were infected with T. cruzi. One hundred sixty-nine patients had CCC, and 76 were asymptomatic. Results Genotype distributions differed between the CCC and asymptomatic groups (chi2 = 9.4; P = .009), with an excess of genotypes with the A allele (AA + AG) in the CCC group. Among patients with CCC, 5% were homozygous for the G allele, compared with 16% of the asymptomatic subjects (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.7-11; P = .001). A similar trend was observed when individuals heterozygous for the G allele were compared with individuals homozygous for the G allele between the CCC and asymptomatic groups (OR, 2.7; 95% CI, 0.97-7.2; P = .026). The A allele seems to confer susceptibility to CCC (OR, 1.9; 95% CI, 1.3-2.9; P = .001). Conclusions The CCL2 variant correlated with a low transcriptional level behaves as a genetic modifier of clinical outcome for T. cruzi infection, and subjects with the CCL2 -2518AA genotype have a 4-fold greater risk of developing CCC than do those without this genotype. |
| Databáze: | OpenAIRE |
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