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

当前位置： X-MOL 学术 › PLOS Pathog. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Whole genome sequencing of extreme phenotypes identifies variants in CD101 and UBE2V1 associated with increased risk of sexually acquired HIV-1.
PLoS Pathogens ( IF 5.5 ) Pub Date : 2017-11-06 , DOI: 10.1371/journal.ppat.1006703
Romel D Mackelprang ₁ , Michael J Bamshad _{2,

3} , Jessica X Chong ₂ , Xuanlin Hou ₁ , Kati J Buckingham ₂ , Kathryn Shively ₂ , Guy deBruyn ₄ , Nelly R Mugo _{1,

5} , James I Mullins _{1,

6,

7} , M Juliana McElrath _{7,

8} , Jared M Baeten _{1,

7,

9} , Connie Celum _{1,

7,

9} , Mary J Emond ₁₀ , Jairam R Lingappa _{1,

2,

9} ,

Affiliation

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

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.

中文翻译：

极端表型的全基因组测序可确定CD101和UBE2V1中的变异与性获得性HIV-1的风险增加有关。

改变HIV-1获得风险的宿主遗传变异可以指导HIV-1预防策略的发展。但是，对稀有或中频变体与HIV-1获取之间的关联还没有很好的研究。我们用全基因组测序数据测试了100个撒哈拉以南非洲人的基因区变异与极端HIV-1采集表型之间的关联。CD101免疫球蛋白样区域的错义变体以及女性中UBE2V1的一种错义/ 5'UTR变体与增加的HIV-1感染风险有关（分别为p = 1.9x10-4和p = 3.7x10-3，复制）。已知这两个基因都会影响宿主的炎症途径。在调整了增加暴露量对获得风险的独立影响之后，效应量随暴露于HIV-1的增加而增加。试验注册ClinicalTrials.gov NCT00194519；NCT00557245。

更新日期：2017-11-07

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11