Distribution of three HIV-1 resistance-conferring polymorphisms (SDF1-3'A, CCR2-641, and CCR5-delta32) in global populations.
Chemokine receptors (CCR5, CXCR4 and CCR2) have been shown to be important co-receptors for HIV infection. Mutations at CCR5 (CCR5-delta2), CCR2 (CCR2-641), and stromal-derived factor SDF1 (SDF1-3'A), a primary ligand for CXCR4, are known to have protective effects against HIV-1 infection and the onset of AIDS symptoms. We studied the three-locus genotype frequency distributions in 70worldwide populations from a sample of 2341 individuals without any known history of HIV-1 infection and AIDS symptoms. From these data, we estimated the risk of AIDS onset (relative hazard, RH) of each population. This survey shows that the substantial allele frequency differences of each of these mutations translate into an extensive variation in relative hazards for AIDS in worldwide populations. However, no evidence of natural selection against the mutant gene carriers is detected. Finally, the combined three-locus genotype data predict the highest relative hazard (RH) in South-East Asia and Africa where AIDS is known to be more prevalent.
Su
B
B
Human Genetics Center, University of Texas, Houston 77030, USA.
Sun
G
G
Lu
D
D
Xiao
J
J
Hu
F
F
Chakraborty
R
R
Deka
R
R
Jin
L
L
D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D005787:Gene Frequency; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D011110:Polymorphism, Genetic; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*
C515334:CCR2 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine