title: Genetic variants in the chemokines and chemokine receptors in Chagas disease.
abstract: Clinical symptoms of Chagas' disease occur in 30% of the individuals infected with Trypanosoma cruzi and are characterised by heart inflammation and dysfunction. Chemokines and chemokine receptors control the migration of leukocytes during the inflammatory process and are involved in the modulation of Th1 or Th2 responses. To determine their influence, we investigated the possible role of CCL5/RANTES and CXCL8/IL8 chemokines, and CCR2 and CCR5 chemokines receptors cluster gene polymorphisms with the development of chagasic cardiomyopathy. Our study included 260 Chagas seropositive individuals (asymptomatic, n=130; cardiomyopathic, n=130) from an endemic area of Colombia. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and TaqMan SNP genotyping assay. We found statistically significant differences in the distribution of the CCR5 human haplogroup (HH)-A (p=0.027; OR=3.78, 95% CI=1.04-13.72). Moreover, we found that the CCR5-2733 G and CCR5-2554 T alleles are associated, respectively, with a reduced risk of susceptibility and severity to develop chagasic cardiomyopathy. No other associations were found to be significant for the other polymorphisms analysed in the CCR5, CCR2, CCL5/RANTES and CXCL8/IL8 genes. Our data suggest that the analysed chemokines and chemokine receptor genetic variants have a weak but important association with the development of chagasic cardiomyopathy in the population under study.
authors.affiliation: Grupo de Inmunología y Epidemiología Molecular, GIEM, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia.
authors.forename: Oscar
authors.initials: O
authors.lastname: Flórez
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.forename: Clara Isabel
authors.initials: CI
authors.lastname: González
mesh_terms: D000328:Adult; D000483:Alleles; D002598:Chagas Cardiomyopathy / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D054390:Receptors, CCR2 / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics*; D014349:Trypanosoma cruzi / Q000502:physiology
chemical_list: C483024:CCL5 protein, human; C515334:CCR2 protein, human; C508606:CXCL8 protein, human; D018946:Chemokine CCL5; D016209:Interleukin-8; D054390:Receptors, CCR2; D019713:Receptors, CCR5