Distribution of two HIV-1-resistant polymorphisms (SDF1-3'A and CCR2-64I) in East Asian and world populations and its implication in AIDS epidemiology.
Chemokine receptor CCR2 and stromal-derived factor (SDF-1) are involved in HIV infection and AIDS symptom onset. Recent cohort studies showed that point mutations in these two genes, CCR2-64I and SDF1-3'A, can delay AIDS onset > or = 16 years after seroconversions. The protective effect of CCR2-64I is dominant, whereas that of SDF1-3'A is recessive. SDF1-3'A homozygotes also showed possible protection against HIV-1 infection. In this study, we surveyed the frequency distributions of the two alleles at both loci in world populations, with emphasis on those in east Asia. The CCR2-64I frequencies do not vary significantly in the different continents, having a range of 0.1-0.2 in most populations. A decreasing cline of the CCR2-64I frequency from north to south was observed in east Asia. In contrast, the distribution of SDF1-3'A in world populations varies substantially, and the highest frequency was observed in Oceanian populations. Moreover, an increasing cline of the SDF1-3'A frequency from north to south was observed in east Asia. The relative hazard values were computed to evaluate the risk of AIDS onset on the basis of two-locus genotypes in the east Asian and world populations.
Su
B
B
Human Genetics Center, University of Texas School of Public Health, Houston, TX 77225, USA.
Jin
L
L
Hu
F
F
Xiao
J
J
Luo
J
J
Lu
D
D
Zhang
W
W
Chu
J
J
Du
R
R
Geng
Z
Z
Qiu
X
X
Xue
J
J
Tan
J
J
O'Brien
S J
SJ
Chakraborty
R
R
D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology* / Q000235:genetics*; D017668:Age of Onset; D000483:Alleles; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D005202:Asia, Eastern / Q000453:epidemiology; D005787:Gene Frequency / Q000235:genetics*; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D010139:Pacific Islands / Q000453:epidemiology; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D016016:Proportional Hazards Models; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics*; D013997:Time Factors
C515334:CCR2 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine