PLoS Pathogens (Nov 2017)

Whole genome sequencing of extreme phenotypes identifies variants in CD101 and UBE2V1 associated with increased risk of sexually acquired HIV-1.

  • Romel D Mackelprang,
  • Michael J Bamshad,
  • Jessica X Chong,
  • Xuanlin Hou,
  • Kati J Buckingham,
  • Kathryn Shively,
  • Guy deBruyn,
  • Nelly R Mugo,
  • James I Mullins,
  • M Juliana McElrath,
  • Jared M Baeten,
  • Connie Celum,
  • Mary J Emond,
  • Jairam R Lingappa,
  • Partners in Prevention HSV/HIV Transmission Study and the Partners PrEP Study Teams

DOI
https://doi.org/10.1371/journal.ppat.1006703
Journal volume & issue
Vol. 13, no. 11
p. e1006703

Abstract

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Host genetic variation modifying HIV-1 acquisition risk can inform development of HIV-1 prevention strategies. However, associations between rare or intermediate-frequency variants and HIV-1 acquisition are not well studied. We tested for the association between variation in genic regions and extreme HIV-1 acquisition phenotypes in 100 sub-Saharan Africans with whole genome sequencing data. Missense variants in immunoglobulin-like regions of CD101 and, among women, one missense/5' UTR variant in UBE2V1, were associated with increased HIV-1 acquisition risk (p = 1.9x10-4 and p = 3.7x10-3, respectively, for replication). Both of these genes are known to impact host inflammatory pathways. Effect sizes increased with exposure to HIV-1 after adjusting for the independent effect of increasing exposure on acquisition risk.Trial registrationClinicalTrials.gov NCT00194519; NCT00557245.