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Basic Science

Global distribution of the CCR2-64I/CCR5-59653T HIV-1 disease-protective haplotype

Martinson, Jeremy J.; Hong, Lilya; Karanicolas, Rosea; Moore, John P.a; Kostrikis, Leondios G.a

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Objectives: Several natural polymorphisms in the genes for the human CC-chemokine receptors CCR5 and CCR2 are associated with HIV-1 disease. The CCR2-64I genetic variant [a G to A substitution resulting in a valine (V) to isoleucine (I) change at position 64] is in strong linkage disequilibrium with a mutation within the CCR5 regulatory region (CCR5-59653T). Individuals with two CCR2-64I alleles are not resistant to sexual transmission of HIV-1, but progress significantly more slowly to HIV-1 disease. It is therefore important to determine the global distributions of CCR2-64I and CCR5-59653T genetic variants and define the degree of linkage between them.

Design and methods: We have developed molecular beacon-based, real-time PCR allele discrimination assays for all three chemokine receptor mutations, and used these spectral genotyping assays to genotype 3923 individuals from a globally distributed set of 53 populations.

Results: CCR2-64I and CCR5-59653T genetic variants are found in almost all populations studied: their allele frequencies are greatest (∼35%) in Africa and Asia but decrease in Northern Europe. We confirm that CCR2-64I is in strong linkage disequilibrium with CCR5-59653T (96.92% of individuals had the same genotype for both CCR2-64I and CCR5-59653T polymorphisms).

Conclusions: The greater geographical distribution of the CCR2-64I/CCR5-59653T haplotype compared with that of CCR5-Δ32 suggests that it is a much older mutation whose origin predates the dispersal of modern humans.

© 2000 Lippincott Williams & Wilkins, Inc.


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