Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr 1;86(4):509-515.
doi: 10.1097/QAI.0000000000002584.

Association of SNPs in HLA-C and ZNRD1 Genes With HIV-1 Mother-to-Child Transmission in Zambia Population

Ronaldo Celerino da Silva  1   2 , Ludovica Segat  3 , Louise Kuhn  4 , José Artur Bogo Chies  5 , Sergio Crovella  1   2
Affiliations

Association of SNPs in HLA-C and ZNRD1 Genes With HIV-1 Mother-to-Child Transmission in Zambia Population

Ronaldo Celerino da Silva et al. J Acquir Immune Defic Syndr. .

Abstract

Background: Human leukocyte antigen C (HLA-C) and Zinc ribbon domain containing 1 (ZNRD1) are considered HIV-1 restriction factors and are expressed in the placenta. Variations in HLA-C and ZNRD1 genes are known to influence HIV-1 infection, including viral replication and progression to AIDS. Little is known about the role of variants in these genes in HIV-1 mother-to-child transmission.

Methods: We evaluated the distribution of HLA-C (rs10484554, rs9264942) and ZNRD1 (rs8321, rs3869068) variants in a Zambian population composed of 333 children born to HIV-1+ mothers (248 HIV-1 noninfected/85 HIV-1 infected) and 97 HIV-1+ mothers.

Results: Genotypic distribution of HLA-C and ZNRD1 were in Hardy-Weinberg equilibrium, except for HLA-C rs10484554 in both groups. In mothers, no significant differences were observed in their allele and genotypic distributions for both genes. The T and TT variants (rs10484554-HLA-C) were significantly more frequent among HIV-1+ children, specifically those who acquired the infection in utero (IU) and intrapartum (IP). For ZNRD1, the T allele (rs3869068) was more frequent in HIV-1- children, showing significant differences in relation to those infected via IP and postpartum (PP). The CT and TT genotypes were significantly more frequent in HIV-1- children.

Conclusions: Variations in HLA-C (T and TT-rs10484554) and ZNRD1 (T and CT/TT-rs3869068) can increase and decrease the susceptibility to HIV-1 infection via mother-to-child transmission, respectively. Further studies are encouraged focusing on a greater number of variants and sample size, with functional validation and in other populations.

Trial registration: ClinicalTrials.gov NCT00310726.

PubMed Disclaimer

Conflict of interest statement

R.C.d.S. is currently receiving a grant of the “Fundação de Aparo à Ciência e Tecnologia do Estado de Pernambuco—FACEPE” (APQ-0077-2.02/17—BCT-0081-2.02/17)” and of the “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES (Programa Nacional de Pós-doutoramento—PNPD no 88882.306352/2018-01) from Brazil. The remaining authors have no conflicts of interest to disclose.

References

    1. Joint United Nations Programme on HIV/AIDS (UNAIDS). UNAIDS Data 2018. Geneva, Switzerland: UNAIDS; 2018.
    1. Luzuriaga K. Mother-to-child transmission of HIV: a global perspective. Curr Infect Dis Rep. 2007;9:511–517.
    1. Smith PD, Meng G, Salazar-Gonzalez JF, et al. Macrophage HIV-1 infection and the gastrointestinal tract reservoir. J Leukoc Biol. 2003;74:642–649.
    1. Boily-Larouche G, Iscache ALL, Zijenah LS, et al. Functional genetic variants in DC-SIGNR are associated with mother-to-child transmission of HIV-1. PLoS One. 2009;4:e7211.
    1. Naarding MA, Ludwig IS, Groot F, et al. Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ T lymphocytes. J Clin Invest. 2005;115:3256–3264.

Publication types

MeSH terms

Associated data