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

PLoS Pathogens

Jessica X. Chong¹  Romel D. Mackelprang²  Kati J. Buckingham²  Jared M. Baeten²  James I. Mullins²  Mary J. Emond³  Jairam R. Lingappa³  Connie Celum⁴  Guy deBruyn⁵  Michael J. Bamshad⁵  Xuanlin Hou⁵  Kathryn Shively⁵  M. Juliana McElrath⁶  Nelly R. Mugo⁷  for the Partners in Prevention HSV/HIV Transmission Study and the Partners PrEP Study Teams⁸ 

[1] Department of Genome Sciences, University of Washington, Seattle, United States of America;Department of Global Health, University of Washington, Seattle, United States of America;Department of Medicine, University of Washington, Seattle, United States of America;Department of Microbiology, University of Washington, Seattle, United States of America;Department of Pediatrics, University of Washington, Seattle, United States of America;Partners in Health Research and Development, Kenya Medical Research Institute, Thika, Kenya;Perinatal HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa;Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

关键词: HIV-1;    Cytokines;    Genome-wide association studies;    Alleles;    Ethnicities;    Viral replication;    Blood plasma;    Regulatory T cells;   

DOI  :  10.1371/journal.ppat.1006703

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY