SNP/haplotype associations of CCR2 and CCR5 genes with severity of chagasic cardiomyopathy.

BACKGROUND

Chronic inflammation plays a major role in the tissue injury seen in the chronic chagasic cardiomyopathy. The CCR2 and CCR5 chemokine receptors are involved with the type of cellular infiltrate present in cardiac tissue and CCR5-gene variants were previously associated with this pathology.

METHODS AND RESULTS

This is a replication study in an independent cohort with larger sample size. Nine SNPs of CCR5 and CCR2 were typified to confirm the association previously found with Chagas disease. Evidence of association with severity was found for the A allele of rs1799864 of CCR2 (pad=0.02; OR=1.91, 95% CI=1.10-3.30), the T allele of the rs1800024 of CCR5 (pad=0.01; OR=1.95, 95% CI=1.13-3.38), and the HHF(∗)2 haplotype (p=0.03, OR=1.65, 95% CI=1.03-2.65). These results were replicated in the study combined with previous data. In this analysis it was replicated the allele T of rs2734648 (pad=0.009, OR=0.52, 95% CI=0.32-0.85) with protection. In addition, the allele G of rs1800023 (pad=0.043, OR=0.61, 95% CI=0.38-0.98), and the HHC haplotype (p=0.004, OR=0.62, 95% CI=0.44-0.86) were also associated with protection. In contrast, the allele A of rs1799864 of CCR2 (pad=0.009; OR=1.90, 95% CI=1.17-3.08); and the allele T of rs1800024 of CCR5 (pad=0.005, OR=1.98, 95% CI=1.22-3.23) were associated with greater severity. No evidence of association between symptomatic and asymptomatic patients was observed.

CONCLUSIONS

These results confirm that variants of CCR5 and CCR2 genes and their haplotypes are associated with the severity but not with susceptibility to develop chagasic cardiomyopathy.