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 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.
['Vega|Jorge A|JA|', 'Villegas-Ospina|Simón|S|', 'Aguilar-Jiménez|Wbeimar|W|', 'Rugeles|María T|MT|', 'Bedoya|Gabriel|G|', 'Zapata|Wildeman|W|']
D015331:Cohort Studies D003105:Colombia D005838:Genotype D015658:HIV Infections D015497:HIV-1 D006239:Haplotypes D006801:Humans D007113:Immunity, Innate D010641:Phenotype D020641:Polymorphism, Single Nucleotide D019713:Receptors, CCR5
haplotypes HIV-1 phenotype Colombia immunity, innate