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Risk for HIV-1 infection associated with a common CXCL12 (SDF1) polymorphism and CXCR4 variation in an African

Desiree C Petersen1, Richard H Glashoff, Sadeep Shrestha

  • 1Department of Medical Virology, University of Stellenbosch, Tygerberg Medical School, South Africa.

Journal of Acquired Immune Deficiency Syndromes (1999)
|November 15, 2005
PubMed

Insights

The SDF1-3'A single nucleotide polymorphism (SNP) in the CXCL12 gene increases HIV-1 infection risk in a South African population. CXCR4 gene mutations were not found to be associated with HIV-1 susceptibility.

Area of Science:

  • Genetics
  • Immunology
  • Virology

Background:

  • CXC chemokine ligand 12 (CXCL12), also known as SDF1, is the sole natural ligand for the HIV-1 coreceptor CXCR4.
  • A specific single nucleotide polymorphism (SNP) in the CXCL12 gene, SDF1-3'A, has shown conflicting associations with AIDS progression.
  • Mutations in the CXCR4 gene are uncommon and have not been linked to HIV-1/AIDS pathogenesis.

Purpose of the Study:

  • To investigate the association between the SDF1-3'A SNP and CXCR4 gene mutations with susceptibility to HIV-1 infection.
  • To analyze genetic factors influencing HIV-1 infection risk in a sub-Saharan African population.

Main Methods:

  • Genotyping of the SDF1-3'A SNP in 257 HIV-1-seropositive and 113 HIV-1-seronegative individuals from the Xhosa ethnic group in South Africa.
  • Mutation screening of polymorphic markers within the CXCR4 gene.
  • Statistical analysis to determine associations between genetic variations and HIV-1 infection risk.

Main Results:

  • The SDF1-3'A SNP was significantly associated with an increased risk of HIV-1 infection (P = 0.0319).
  • No significant association was found between the SDF1-3'A SNP and plasma levels of CXCL12.
  • Mutation analysis revealed high genetic conservation in the coding region of the CXCR4 gene within this population.

Conclusions:

  • The SDF1-3'A SNP is a potential genetic risk factor for HIV-1 infection in the studied South African population.
  • The CXCR4 gene appears genetically conserved and not significantly implicated in HIV-1 susceptibility in this group.

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