title: The monocyte chemoattractant protein-1 gene polymorphism is associated with cardiomyopathy in human chagas disease.
abstract: 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.
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), São Paulo, SP, Brazil. ramasawm@usp.br
authors.forename: Rajendranath
authors.initials: R
authors.lastname: Ramasawmy
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
authors.forename: Kellen C
authors.initials: KC
authors.lastname: Fae
authors.forename: Fernanda G
authors.initials: FG
authors.lastname: Martello
authors.forename: Natalie G
authors.initials: NG
authors.lastname: Müller
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Cavalcanti
authors.forename: Barbara
authors.initials: B
authors.lastname: Ianni
authors.forename: Charles
authors.initials: C
authors.lastname: Mady
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Anna C
authors.initials: AC
authors.lastname: Goldberg
mesh_terms: D000368:Aged; D002598:Chagas Cardiomyopathy / Q000235:genetics*; D018932:Chemokine CCL2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D018932:Chemokine CCL2