Journal Article

The Monocyte Chemoattractant Protein–1 Gene Polymorphism Is Associated with Cardiomyopathy in Human Chagas Disease

Rajendranath Ramasawmy, Edecio Cunha-Neto, Kellen C. Faé, Fernanda G. Martello, Natalie G. Müller, Vanessa L. Cavalcanti, Barbara Ianni, Charles Mady, Jorge Kalil and Anna C. Goldberg

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 43, issue 3, pages 305-311
Published in print August 2006 | ISSN: 1058-4838
Published online August 2006 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/505395
The Monocyte Chemoattractant Protein–1 Gene Polymorphism Is Associated with Cardiomyopathy in Human Chagas Disease

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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/nitic 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 (χ2 = 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.

Journal Article.  4612 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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