title: Global distribution of the CCR2-64I/CCR5-59653T HIV-1 disease-protective haplotype.
abstract: 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.
authors.affiliation: Department of Biological Anthropology, Oxford University, UK.
authors.forename: J J
authors.initials: JJ
authors.lastname: Martinson
authors.forename: L
authors.initials: L
authors.lastname: Hong
authors.forename: R
authors.initials: R
authors.lastname: Karanicolas
authors.forename: J P
authors.initials: JP
authors.lastname: Moore
authors.forename: L G
authors.initials: LG
authors.lastname: Kostrikis
mesh_terms: 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
chemical_list: C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine