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


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 (approximately 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-delta32 suggests that it is a much older mutation whose origin predates the dispersal of modern humans.
Martinson
J J
JJ
Department of Biological Anthropology, Oxford University, UK.
Hong
L
L
Karanicolas
R
R
Moore
J P
JP
Kostrikis
L G
LG
D000483:Alleles; D005820:Genetic Testing; D014943:Global Health; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000032:analysis*; D019707:Receptors, Chemokine / Q000032:analysis* / Q000235:genetics
C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine