Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections
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Author
Vergara, Candelaria
Thio, Chloe
Latanich, Rachel
Cox, Andrea L.
Kirk, Gregory D.
Mehta, Shruti H.
Busch, Michael
Murphy, Edward L
Villacres, Maria C.
Peters, Marion G.
French, Audrey L.
Golub, Elizabeth
Eron, Joseph
Lahiri, Cecile Delille
Shrestha, Sadeep
Gustafson, Deborah
Young, Mary
Anastos, Kathryn
Aouizerat, Bradley
Thomas, David L.
Duggal, Priya
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/gene.2017.2Metadata
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Vergara, C., C. Thio, R. Latanich, A. L. Cox, G. D. Kirk, S. H. Mehta, M. Busch, et al. 2016. “Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections.” Genes and immunity 18 (2): 82-87. doi:10.1038/gene.2017.2. http://dx.doi.org/10.1038/gene.2017.2.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-1 (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. 1538 participants with active HIV and/or HCV infection in 3 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 logIL-18 including HCV and HIV infection status and HIV-RNA, in each ancestry group and then meta-analyzed. Eleven highly correlated SNPs (r2=0.98-1) in the IL18-BCO2 region were significantly associated with logIL-18; Each T allele of rs80011693 confers a decrease of 0.06 log pg/mL of IL-18 after adjusting for covariates (rs80011693; rs111311302 β=-0.06, P-value=2.7×10-4). In conclusion, genetic variation in IL18 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408324/pdf/Terms of Use
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