title: Effect of chemokine receptor mutations on heterosexual human immunodeficiency virus transmission.
abstract: To assess the effect of mutations at the CCR-2 and CCR-5 loci on heterosexual human immunodeficiency virus (HIV) transmission, 144 persons heterosexually exposed to HIV (infected and uninfected [EU]) and 57 HIV-positive index partners were genotyped. A significantly higher frequency of 64I heterozygotes at CCR-2 was observed in HIV-positive than in EU women (P=.02, relative risk=1.6). The allele frequency of 64I in women was 8% in HIV-positive contacts and 1% in EUs (P<.02). At CCR-5, no difference in the frequency of Delta32 was seen between groups, and the CCR-5 genotypes did not differ in accumulated "at-risk" exposure in EUs. Combining the analysis of the Delta32 and 64I mutations in index partners suggested an additive effect on transmission (P=.10). Thus heterozygosity for 64I at CCR-2 acts as a risk factor for HIV infection of women after heterosexual contact but heterozygosity for Delta32 at CCR-5 has no detectable effect.
authors.affiliation: Centre for HIV Research, Institute of Cell, Animal, and Population Biology, University of Edinburgh, Edinburgh, Scotland.
authors.forename: S F
authors.initials: SF
authors.lastname: Lockett
authors.forename: A
authors.initials: A
authors.lastname: Alonso
authors.forename: R
authors.initials: R
authors.lastname: Wyld
authors.forename: M P
authors.initials: MP
authors.lastname: Martin
authors.forename: J R
authors.initials: JR
authors.lastname: Robertson
authors.forename: S M
authors.initials: SM
authors.lastname: Gore
authors.forename: C L
authors.initials: CL
authors.lastname: Leen
authors.forename: R P
authors.initials: RP
authors.lastname: Brettle
authors.forename: D L
authors.initials: DL
authors.lastname: Yirrell
authors.forename: M
authors.initials: M
authors.lastname: Carrington
authors.forename: A J
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000235:genetics / Q000635:transmission*; D006679:HIV Seropositivity / Q000235:genetics / Q000635:transmission*; D020010:Heterosexuality; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D012307:Risk Factors
chemical_list: C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine