Narrowing the Relationship between Human CCR5 Gene Polymorphisms and Chagas Disease: Systematic Review and Meta-Analysis

Abstract

Our aim was to carry out a qualitative and quantitative synthesis of the influence of CCR5 genetic variants on Chagas disease (CD) through a systematic review. A total of 1197 articles were analyzed, and eleven were included in the review. A meta-analysis was conducted along with principal component analyses (PCAs). The polymorphisms found were analyzed using the SNP2TFBS tool to identify possible variants that influence the interaction with gene binding sites. Eleven studied variants were identified: rs2856758, rs2734648, rs1799987, rs1799988, rs41469351, rs1800023, rs1800024, Δ32/rs333, rs3176763, rs3087253 and rs11575815. The studies analyzed were published between 2001 and 2019, conducted in Argentina, Brazil, Spain, Colombia and Venezuela, and included Argentine, Brazilian, Colombian, Peruvian and Venezuelan patients. Eight polymorphisms were subjected to the meta-analysis, of which six were associated with the development of the cardiac form of CD: rs1799987—G/G and G/A in the dominance model and G/G in the recessiveness model; rs2856758—A/G in the codominance model; rs2734648—T/T and T/G in the dominance model; rs1799988—T/T in both the codominance and recessiveness models; rs1800023—G allele and the G/G genotype in the codominance and recessiveness models, and the G/G and G/A genotypes in the dominance model; and rs1800024—T allele. The PCA analyses were able to indicate the relationships between the alleles and the genotypes of the polymorphisms. The SNP2TFBS tool identified rs1800023 as an influencer of the Spi1 transcription factor (p < 0.05). A correlation was established between the alleles associated with the cardiac form of CD in this review, members of the C haplotype of the gene (HHC–TGTG), and the cardiac form of CD.

Keywords

• American trypanosomiasis
• SNPs
• chemokines