A whole genome association study of mother-to-child transmission of HIV in Malawi

Bonnie R Joubert,Steven R Meshnick,Victor Mwapasa,Nora Franceschini,Kari E North,Ethan M Lange

doi:10.1186/gm138

Bonnie R Joubert, Steven R Meshnick + Show 4 more

Open Access

https://doi.org/10.1186/gm138

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Abstract

BackgroundMore than 300,000 children are newly infected with HIV each year, predominantly through mother-to-child transmission (HIV MTCT). Identification of host genetic traits associated with transmission may more clearly explain the mechanisms of HIV MTCT and further the development of a vaccine to protect infants from infection. Associations between transmission and a selection of genes or single nucleotide polymorphisms (SNP)s may give an incomplete picture of HIV MTCT etiology. Thus, this study employed a genome-wide association approach to identify novel variants associated with HIV MTCT.MethodsWe conducted a nested case-control study of HIV MTCT using infants of HIV(+) mothers, drawn from a cohort study of malaria and HIV in pregnancy in Blantyre, Malawi. Whole genome scans (650,000 SNPs genotyped using Illumina genotyping assays) were obtained for each infant. Logistic regression was used to evaluate the association between each SNP and HIV MTCT.ResultsGenotype results were available for 100 HIV(+) infants (at birth, 6, or 12 weeks) and 126 HIV(-) infants (at birth, 6, and 12 weeks). We identified 9 SNPs within 6 genes with a P-value < 5 × 10-5 associated with the risk of transmission, in either unadjusted or adjusted by maternal HIV viral load analyses. Carriers of the rs8069770 variant allele were associated with a lower risk of HIV MTCT (odds ratio = 0.27, 95% confidence interval = 0.14, 0.51), where rs8069770 is located within HS3ST3A1, a gene involved in heparan sulfate biosynthesis. Interesting associations for SNPs located within or near genes involved in pregnancy and development, innate immunological response, or HIV protein interactions were also observed.ConclusionsThis study used a genome-wide approach to identify novel variants associated with the risk of HIV MTCT in order to gain new insights into HIV MTCT etiology. Replication of this work using a larger sample size will help us to differentiate true positive findings.

Highlights

More than 300,000 children are newly infected with HIV each year, predominantly through motherto-child transmission (HIV mother-to-child transmission (MTCT))
We report the effects of single nucleotide polymorphisms (SNP) within genes known to be associated with HIV/ AIDS, for the purposes of replication in our study population
Association results no genome-wide significant SNPs were detected (P < 1 × 10-7), we identified nine SNPs within six genes with a P-value

Summary

Introduction

More than 300,000 children are newly infected with HIV each year, predominantly through motherto-child transmission (HIV MTCT). A larger wealth of research describes genetic associations with adult HIV transmission and progression to AIDS. The CCR5 coreceptor binds with chemokines produced by CD8+ T cells, including RANTES (CCL5), and MIP (macrophage inflammatory protein) 1α (CCL3) and 1β (CCL4). Higher concentrations of these ligands have been associated with a lower risk of HIV-1 infection and progression to AIDS, likely through competition with R5 strains of HIV for binding with the CCR5 receptor, preventing HIV from entering the cell and replicating [3,4,5,6,7,8]. CCL3L1 copy number variation has been associated with HIV/AIDS progression in adults [10,14,15,16]

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