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

Am J Hum Genet. 1999 Oct;65(4):1047-53. doi: 10.1086/302568.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / epidemiology*
  • Acquired Immunodeficiency Syndrome / genetics*
  • Age of Onset
  • Alleles
  • Asia, Eastern / epidemiology
  • Chemokine CXCL12
  • Chemokines, CXC / genetics*
  • Gene Frequency / genetics*
  • Genes, Dominant / genetics
  • Genes, Recessive / genetics
  • Genetic Predisposition to Disease / genetics
  • HIV-1 / physiology
  • Humans
  • Pacific Islands / epidemiology
  • Point Mutation / genetics
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Restriction Fragment Length
  • Prevalence
  • Proportional Hazards Models
  • Receptors, CCR2
  • Receptors, Chemokine*
  • Receptors, Cytokine / genetics*
  • Time Factors

Substances

  • CCR2 protein, human
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Receptors, CCR2
  • Receptors, Chemokine
  • Receptors, Cytokine