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

Abstract

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.

The effect of combined polymorphisms in chemokines and chemokine receptors on the clinical course of HIV-1 infection in a Brazilian population

“…The polymorphisms analysed in this study exhibit variable frequencies in distinct populations (Smith et al 1997, McDermott et al 1998, Su et al 1999, Gonzalez et al 2001. As mentioned previously, the Brazilian population has a complex genetic background (CallegariJacques et al 2003, Pena 2005.…”

“…However, other studies did not find such a correlation (Ioannidis et al 2001, Watanabe et al 2003, Reiche et al 2006, while a third group of studies found a correlation with accelerated disease progression (Mummidi et al 1998, van Rij et al 1998, Daar et al 2005. SDF1-3'A distribution varies significantly between different populations, with frequencies from 2-9% in Africans and up to 54-71% in Oceania (Su et al 1999).…”

“…CCR5-∆32, CCR2-64I, CCR5-59029A and SDF1-3'A all exhibit variable frequencies in distinct populations (Smith et al 1997, McDermott et al 1998, Su et al 1999, Gonzalez et al 2001 and, possibly, their phenotypes depend on the ethnicity analysed (Mummidi et al 1998, Gonzalez et al 1999. The Brazilian population presents a complex genetic background, characterised by a high degree of miscegenation (Callegari-Jacques et al 2003, Pena 2005.…”

Distribution of three HIV-1 resistance-conferring polymorphisms (SDF1-3′A, CCR2-64I, and CCR5-Δ32) in global populations

“…18 We contend that the resulting intermediate frequencies of the two mutant alleles combined with complete absence of the CCR5-∆32, yielded the high RH values in Southeast Asian populations, which coincide with the high prevalence and rapid growth of HIV infections in this area. 15 It is important to point out that the estimation of RH indices may not be accurate given the width of the 95% confidence intervals (see Table 1 in Winkler et al).…”

“…Such *Data published in our previous study on SDF1-3'A and CCR2-64I. 18 Standard errors are shown in parentheses. Populations with numbers 1, 2 or 3 were sampled in different geographic locations of the same country.…”