Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort

• Published in: Biomédica Vol. 37; no. 2; pp. 267 - 273
• Main Authors: Vega, Jorge A, Villegas-Ospina, Simón, Aguilar-Jiménez, Wbeimar, Rugeles, María T, Bedoya, Gabriel, Zapata, Wildeman
• Format: Journal Article
• Language: English
• Published: Colombia Instituto Nacional de Salud 01.06.2017
• Subjects: Cohort Studies; Colombia; Genotype; haplotypes; Haplotypes - genetics; HIV Infections - epidemiology; HIV Infections - genetics; HIV Infections - microbiology; HIV-1; HIV-1 - chemistry; HIV-1 - genetics; HIV-1 - immunology; Humans; immunity, innate; Immunity, Innate - immunology; Immunity, Innate - physiology; Phenotype; Polymorphism, Single Nucleotide - genetics; Polymorphism, Single Nucleotide - physiology; Receptors, CCR5 - genetics; TROPICAL MEDICINE; HIV-1; phenotype; Colombia; haplotypes; immunity, innate; fenotipo; haplotipos; HIV-1, inmunidad innata
• ISSN: 0120-4157; 0120-4157
• DOI: 10.7705/biomedica.v37i3.3237

Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls). Haplotypes were inferred using the Arlequin software, and their frequency in individual or combined loci was compared between cases and controls by the chi-square test. A p' value ;0.05 after Bonferroni correction was considered significant. Homozygosis of the human haplogroup (HH) E was absent in controls and frequent in cases, showing a tendency to susceptibility. The haplotypes C-C and T-T in CCL3 were associated with susceptibility (p'=0.016) and resistance (p';0.0001) to HIV-1 infection, respectively. Finally, in multilocus analysis, the haplotype combinations formed by HHC in CCR5-CCR2, T-T in CCL3 and G-C in CCL5 were associated with resistance (p'=0.006). Our results suggest that specific combinations of variants in genes from the same signaling pathway can define an HIV-1 resistant phenotype. Despite our small sample size, our statistically significant associations suggest strong effects; however, these results should be further validated in larger cohorts.