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Genes Immun. 2017 Mar;18(2):82-87. doi: 10.1038/gene.2017.2. Epub 2017 Mar 16.

Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections.

Author information

1
School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
2
Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
3
University of California, San Francisco, CA, USA.
4
Blood Systems Research Institute, San Francisco, CA, USA.
5
Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
6
CORE Center/Stroger Hospital of Cook County, Chicago, IL, USA.
7
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
8
School of Medicine, Emory University, Atlanta, GA, USA.
9
The University of Alabama at Birmingham, AL, USA.
10
State University of New York-Downstate Medical Center, New York, NY, USA.
11
Georgetown University Medical Center, Washington, DC, USA.
12
Albert Einstein College of Medicine and Montefiore Medical Center, New York, NY, USA.
13
Bluestone Center for Clinical Research, New York University, New York, NY, USA.
14
Department of Oral and Maxillofacial Surgery, New York University, New York, NY, USA.
15
Massachusetts General Hospital, Boston, MA, USA.
16
Harvard Medical School, Boston, MA, USA.

Abstract

Inflammasomes are multi-protein complexes integrating pathogen-triggered signaling leading to the generation of pro-inflammatory cytokines including interleukin-18 (IL-18). Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are associated with elevated IL-18, suggesting inflammasome activation. However, there is marked person-to-person variation in the inflammasome response to HCV and HIV. We hypothesized that host genetics may explain this variation. To test this, we analyzed the associations of plasma IL-18 levels and polymorphisms in 10 genes in the inflammasome cascade. About 1538 participants with active HIV and/or HCV infection in three ancestry groups are included. Samples were genotyped using the Illumina Omni 1-quad and Omni 2.5 arrays. Linear regression analyses were performed to test the association of variants with log IL-18 including HCV and HIV infection status, and HIV RNA in each ancestry group and then meta-analyzed. Eleven highly correlated single-nucleotide polymorphisms (r2=0.98-1) in the IL-18-BCO2 region were significantly associated with log IL-18; each T allele of rs80011693 confers a decrease of 0.06 log pg ml-1 of IL-18 after adjusting for covariates (rs80011693; rs111311302 β=-0.06, P-value=2.7 × 10-4). In conclusion, genetic variation in IL-18 is associated with IL-18 production in response to HIV and HCV infection, and may explain variability in the inflammatory outcomes of chronic viral infections.

PMID:
28300059
PMCID:
PMC5408324
DOI:
10.1038/gene.2017.2
[Indexed for MEDLINE]
Free PMC Article

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