title: Polymorphisms in the gene for lymphotoxin-alpha predispose to chronic Chagas cardiomyopathy.
abstract: BACKGROUND
  Chagas disease, caused by Trypanosoma cruzi infection, displays clinical heterogeneity and may be attributable to differential genetic susceptibility. Chronic Chagas cardiomyopathy (CCC) develops only in a subset of T. cruzi-infected individuals and may lead to heart failure that has a worse clinical course and that leads to reduced life expectancy, compared with heart failure of other etiologies. Proinflammatory cytokines play a key role in the development of CCC. Clinical, genetic, and epidemiological studies have linked lymphotoxin-alpha (LTA), a proinflammatory cytokine, to coronary artery disease and myocardial infarction.
  
  
  METHODS
  We used polymerase chain reaction to genotype the LTA +80A-->C and LTA +252A-->G variants in 169 patients with CCC and in 76 T. cruzi-infected asymptomatic (ASY) patients.
  
  
  RESULTS
  Homozygosity with respect to the LTA +80C and LTA +252G alleles was significantly more frequent in the patients with CCC than in the ASY patients (homozygosity for LTA +80C, 47% vs. 33%; homozygosity for LTA +252G, 16% vs. 8%). Haplotype LTA +80A-252A was associated with protection against CCC, whereas haplotype LTA +80C-252G was associated with susceptibility to CCC. Furthermore, homozygosity for the LTA +80A allele correlated with the lowest levels of plasmatic tumor-necrosis factor-alpha.
  
  
  CONCLUSIONS
  Our results suggest that the study of genetic variations in patients with Chagas disease may help in the identification of individuals at increased risk of progressing to CCC and, by providing early treatment, reduce the morbidity and mortality associated with this disease.
authors.affiliation: Heart Institute (InCor), Department of Clinical Medicine, University of São Paulo School of Medicine, São Paulo, Brazil. ramasawm@usp.br
authors.forename: Rajendranath
authors.initials: R
authors.lastname: Ramasawmy
authors.forename: Kellen C
authors.initials: KC
authors.lastname: Fae
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
authors.forename: Natalie G
authors.initials: NG
authors.lastname: Müller
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Cavalcanti
authors.forename: Renata C
authors.initials: RC
authors.lastname: Ferreira
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Drigo
authors.forename: Barbara
authors.initials: B
authors.lastname: Ianni
authors.forename: Charles
authors.initials: C
authors.lastname: Mady
authors.forename: Anna C
authors.initials: AC
authors.lastname: Goldberg
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000097:blood / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008233:Lymphotoxin-alpha / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014349:Trypanosoma cruzi / Q000254:growth & development* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
chemical_list: D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha