title: Influence of intragenic CCL3 haplotypes and CCL3L copy number in HIV-1 infection in a sub-Saharan African population.
abstract: Two CCL3 haplotypes (HapA1 and Hap-A3) and two polymorphic positions shared by the haplotypes (Hap-2SNP (single nucleotide polymorphism)) were investigated together with CCL3L copy number (CN), for their role in HIV-1 disease. Hap-A1 was associated with protection from in utero HIV-1 infection: exposed uninfected (EU) infants had higher representation of wild type (WT)/Hap-A1 than infected infants (excluding intrapartum (IP)-infected infants), which maintained significance post maternal Nevirapine (mNVP) and viral load (MVL) correction (P=0.04; odds ratio (OR)=0.33). Mother-infant pair analyses showed the protective effect of Hap-A1 is dependent on its presence in the infant. Hap-A3 was associated with increased IP transmission: WT/Hap-A3 was increased in IP-transmitting vs non-transmitting (NT) mothers, and remained significant post mNVP and MVL correction (P=0.02; OR=3.50). This deleterious effect of Hap-A3 seemed dependent on its presence in the mother. Hap-2SNP was associated with lower CD4 count in the NT mothers (P=0.03). CCL3 Hap-A1 was associated with high CCL3L CN in total (P=0.001) and EU infants (P=0.006); the effect was not additive, however, having either Hap-A1 or high CCL3L CN was more significantly (P=0.0008) associated with protection from in utero infection than Hap-A1 (P=0.028) or high CCL3L CN (P=0.002) alone. Linkage disequilibrium between Hap-A1 and high CCL3L CN appears unlikely given that a Nigerian population showed an opposite relationship.
authors.affiliation: Centre for HIV and STIs: Cell Biology, National Institute for Communicable Diseases, National Health Laboratory Services, Johannesburg, South Africa. paxim@nicd.ac.za
authors.forename: M
authors.initials: M
authors.lastname: Paximadis
authors.forename: D B
authors.initials: DB
authors.lastname: Schramm
authors.forename: G E
authors.initials: GE
authors.lastname: Gray
authors.forename: G
authors.initials: G
authors.lastname: Sherman
authors.forename: A
authors.initials: A
authors.lastname: Coovadia
authors.forename: L
authors.initials: L
authors.lastname: Kuhn
authors.forename: C T
authors.initials: CT
authors.lastname: Tiemessen
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015704:CD4 Antigens / Q000097:blood; D054405:Chemokine CCL3 / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000635:transmission* / Q000821:virology; D015497:HIV-1; D006239:Haplotypes; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D015810:Linkage Disequilibrium; D019829:Nevirapine / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; C515429:CCL3 protein, human; D015704:CD4 Antigens; D054405:Chemokine CCL3; D019829:Nevirapine