Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort
Introduction: 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 mul...
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| Format: | Article |
| Language: | English |
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Instituto Nacional de Salud
2017-06-01
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| Series: | Biomédica: revista del Instituto Nacional de Salud |
| Subjects: | |
| Online Access: | https://www.revistabiomedica.org/index.php/biomedica/article/view/3237 |
| _version_ | 1818171930965966848 |
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| author | Jorge A. Vega Simón Villegas-Ospina Wbeimar Aguilar-Jiménez María T. Rugeles Gabriel Bedoya Wildeman Zapata |
| author_facet | Jorge A. Vega Simón Villegas-Ospina Wbeimar Aguilar-Jiménez María T. Rugeles Gabriel Bedoya Wildeman Zapata |
| author_sort | Jorge A. Vega |
| collection | DOAJ |
| description | Introduction: 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 CCL5 were 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. |
| first_indexed | 2024-12-11T19:04:33Z |
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| id | doaj.art-85f820fe9ff9446bae9c255ee308f817 |
| institution | Directory Open Access Journal |
| issn | 0120-4157 0120-4157 |
| language | English |
| last_indexed | 2024-12-11T19:04:33Z |
| publishDate | 2017-06-01 |
| publisher | Instituto Nacional de Salud |
| record_format | Article |
| series | Biomédica: revista del Instituto Nacional de Salud |
| spelling | doaj.art-85f820fe9ff9446bae9c255ee308f8172022-12-22T00:53:56ZengInstituto Nacional de SaludBiomédica: revista del Instituto Nacional de Salud0120-41570120-41572017-06-0137226727310.7705/biomedica.v37i3.32371980Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohortJorge A. Vega0Simón Villegas-Ospina1Wbeimar Aguilar-Jiménez2María T. Rugeles3Gabriel Bedoya4Wildeman Zapata5Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia Laboratorio de Genética, Dirección Regional Noroccidente, Instituto Nacional de Medicina Legal y Ciencias Forenses, Medellín, Colombia Genética Molecular, Instituto de Biología, Universidad de Antioquia, Medellín, ColombiaGrupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaGrupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaGrupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaGenética Molecular, Instituto de Biología, Universidad de Antioquia, Medellín, ColombiaGrupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, ColombiaIntroduction: 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 CCL5 were 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.https://www.revistabiomedica.org/index.php/biomedica/article/view/3237HIV-1immunity, innatephenotypehaplotypesColombia |
| spellingShingle | Jorge A. Vega Simón Villegas-Ospina Wbeimar Aguilar-Jiménez María T. Rugeles Gabriel Bedoya Wildeman Zapata Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort Biomédica: revista del Instituto Nacional de Salud HIV-1 immunity, innate phenotype haplotypes Colombia |
| title | Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort |
| title_full | Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort |
| title_fullStr | Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort |
| title_full_unstemmed | Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort |
| title_short | Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort |
| title_sort | haplotypes in ccr5 ccr2 ccl3 and ccl5 are associated with natural resistance to hiv 1 infection in a colombian cohort |
| topic | HIV-1 immunity, innate phenotype haplotypes Colombia |
| url | https://www.revistabiomedica.org/index.php/biomedica/article/view/3237 |
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