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PLoS Pathog. 2017 Nov 6;13(11):e1006703. doi: 10.1371/journal.ppat.1006703. eCollection 2017 Nov.

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

Author information

1
Department of Global Health, University of Washington, Seattle, United States of America.
2
Department of Pediatrics, University of Washington, Seattle, United States of America.
3
Department of Genome Sciences, University of Washington, Seattle, United States of America.
4
Perinatal HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa.
5
Partners in Health Research and Development, Kenya Medical Research Institute, Thika, Kenya.
6
Department of Microbiology, University of Washington, Seattle, United States of America.
7
Department of Medicine, University of Washington, Seattle, United States of America.
8
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America.
9
Department of Epidemiology, University of Washington, Seattle, United States of America.
10
Department of Biostatistics, University of Washington, Seattle, United States of America.

Abstract

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 REGISTRATION:

ClinicalTrials.gov NCT00194519; NCT00557245.

PMID:
29108000
PMCID:
PMC5690691
DOI:
10.1371/journal.ppat.1006703
[Indexed for MEDLINE]
Free PMC Article
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