Jorge A Vega1,2,3, Simón Villegas-Ospina1, Wbeimar Aguilar-Jiménez1, María T Rugeles1, Gabriel Bedoya3, Wildeman Zapata1,4. 1. Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia 2. Laboratorio de Genética, Dirección Regional Noroccidente, Instituto Nacional de Medicina Legal y Cienciaszzm321990Forenses, Medellín, Colombia 3. Genética Molecular, Instituto de Biología, Universidad de Antioquia, Medellín, Colombia 4. Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia
Abstract
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.
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.
Authors: Bo Jia; Xiao-Ling Qiu; Hong-Xing Chu; Xiang Sun; Jie Pan; Zhi-Ping Wang; Jian-Jiang Zhao Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2017-08-20
Authors: Hager Mohamed; Theodore Gurrola; Rachel Berman; Mackenzie Collins; Ilker K Sariyer; Michael R Nonnemacher; Brian Wigdahl Journal: Front Immunol Date: 2022-01-20 Impact factor: 7.561
Authors: Lizdany Flórez-Álvarez; Yurany Blanquiceth; Katherin Ramírez; Ana Claudia Ossa-Giraldo; Paula A Velilla; Juan C Hernandez; Wildeman Zapata Journal: Front Immunol Date: 2020-09-11 Impact factor: 7.561