Effect of chemokine receptor mutations on heterosexual human immunodeficiency virus transmission.
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.
Lockett
S F
SF
Centre for HIV Research, Institute of Cell, Animal, and Population Biology, University of Edinburgh, Edinburgh, Scotland.
Alonso
A
A
Wyld
R
R
Martin
M P
MP
Robertson
J R
JR
Gore
S M
SM
Leen
C L
CL
Brettle
R P
RP
Yirrell
D L
DL
Carrington
M
M
Brown
A J
AJ
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
C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine