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Influence of intragenic CCL3 haplotypes and CCL3L copy number in HIV-1 infection in a sub-Saharan African population

Genes & Immunity volume 14, pages 42–51 (2013)Cite this article

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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.

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Acknowledgements

This study was supported in part by grants from the South African AIDS Vaccine Initiative, NICHD (HD 42402, HD 36177) and Wellcome Trust (076352/Z/05/Z).

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Authors and Affiliations

  1. Centre for HIV and STIs: Cell Biology, National Institute for Communicable Diseases, National Health Laboratory Services, Johannesburg, South Africa

    M Paximadis, D B Schramm & C T Tiemessen

  2. Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    M Paximadis, D B Schramm & C T Tiemessen

  3. Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, Soweto, South Africa

    G E Gray

  4. Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    G Sherman

  5. National Health Laboratory Services, Johannesburg, South Africa

    G Sherman

  6. Empilweni Clinic, Coronation Women and Children Hospital, Enhancing Childhood HIV Outcomes (ECHO), University of the Witwatersrand, Johannesburg, South Africa

    A Coovadia

  7. Department of Epidemiology, College of Physicians and Surgeons, Gertrude H. Sergievsky Centre, Mailman School of Public Health, Columbia University, New York, NY, USA

    L Kuhn

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  1. M Paximadis
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Correspondence to M Paximadis.

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Paximadis, M., Schramm, D., Gray, G. et al. Influence of intragenic CCL3 haplotypes and CCL3L copy number in HIV-1 infection in a sub-Saharan African population. Genes Immun 14, 42–51 (2013). https://doi.org/10.1038/gene.2012.51

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