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

ABSTRACT: ntroduction: 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.Objective: 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.Materials and methods: 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.Results: 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 CCL5were associated with resistance (p’=0.006).Conclusion: 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.

• Autores: Vega Parra, Jorge Arturo; Villegas Ospina, Simón; Aguilar Jiménez, Wbeimar; Rugeles López, María Teresa; Bedoya Berrío, Gabriel de Jesús; Zapata Builes, Wildeman
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2017
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/30908
• Acceso en línea: https://hdl.handle.net/10495/30908; https://revistabiomedica.org/index.php/biomedica/article/view/3237
• Palabra clave: VIH-1; HIV-1; Inmunidad, innata; Immunity, innate; Fenotipo; Phenotype; Haplotipos; Haplotypes; Colombia; http://vocabularies.unesco.org/thesaurus/concept771; https://id.nlm.nih.gov/mesh/D015497; https://id.nlm.nih.gov/mesh/D007113; https://id.nlm.nih.gov/mesh/D010641; https://id.nlm.nih.gov/mesh/D006239
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-nd/2.5/co/