title: Risk for HIV-1 infection associated with a common CXCL12 (SDF1) polymorphism and CXCR4 variation in an African population.
abstract: CXC chemokine ligand 12 (CXCL12), or stromal cell-derived factor 1 (SDF1), is the only known natural ligand for the HIV-1 coreceptor, CXC chemokine receptor 4 (CXCR4). A single nucleotide polymorphism (SNP) in the CXCL12 gene (SDF1-3'A) has been associated with disease progression to AIDS in some studies, but not others. Mutations in the CXCR4 gene are generally rare and have not been implicated in HIV-1/AIDS pathogenesis. This study analyzed the SDF1-3'A SNP and performed mutation screening for polymorphic markers in the CXCR4 gene to determine the presence or absence of significant associations with susceptibility to HIV-1 infection. The study consisted of 257 HIV-1-seropositive patients and 113 HIV-1-seronegative controls representing a sub-Saharan African population belonging to the Xhosa ethnic group of South Africa. The SDF1-3'A SNP was associated with an increased risk for HIV-1 infection (P = 0.0319) whereas no significant association was observed between the occurrence of the SDF1-3'A SNP and increased or decreased plasma levels of CXCL12. Comprehensive mutation analysis of the CXCR4 gene confirmed a high degree of genetic conservation within the coding region of this ancient population.
authors.affiliation: Department of Medical Virology, University of Stellenbosch, Tygerberg Medical School, South Africa.
authors.forename: Desiree C
authors.initials: DC
authors.lastname: Petersen
authors.forename: Richard H
authors.initials: RH
authors.lastname: Glashoff
authors.forename: Sadeep
authors.initials: S
authors.lastname: Shrestha
authors.forename: Julie
authors.initials: J
authors.lastname: Bergeron
authors.forename: Annette
authors.initials: A
authors.lastname: Laten
authors.forename: Bert
authors.initials: B
authors.lastname: Gold
authors.forename: Estrelita Janse
authors.initials: EJ
authors.lastname: van Rensburg
authors.forename: Michael
authors.initials: M
authors.lastname: Dean
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hayes
mesh_terms: D044383:Black People; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D019718:Receptors, CXCR4 / Q000235:genetics*; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4