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Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections.
Vergara, C; Thio, C; Latanich, R; Cox, A L; Kirk, G D; Mehta, S H; Busch, M; Murphy, E L; Villacres, M C; Peters, M G; French, A L; Golub, E; Eron, J; Lahiri, C D; Shrestha, S; Gustafson, D; Young, M; Anastos, K; Aouizerat, B; Kim, A Y; Lauer, G; Thomas, D L; Duggal, P.
Affiliation
  • Vergara C; School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Thio C; School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Latanich R; School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Cox AL; School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Kirk GD; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
  • Mehta SH; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
  • Busch M; University of California, San Francisco, CA, USA.
  • Murphy EL; University of California, San Francisco, CA, USA.
  • Villacres MC; Blood Systems Research Institute, San Francisco, CA, USA.
  • Peters MG; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • French AL; Blood Systems Research Institute, San Francisco, CA, USA.
  • Golub E; CORE Center/Stroger Hospital of Cook County, Chicago, IL, USA.
  • Eron J; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
  • Lahiri CD; University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Shrestha S; School of Medicine, Emory University, Atlanta, GA, USA.
  • Gustafson D; The University of Alabama at Birmingham, AL, USA.
  • Young M; State University of New York-Downstate Medical Center, New York, NY, USA.
  • Anastos K; Georgetown University Medical Center, Washington, DC, USA.
  • Aouizerat B; Albert Einstein College of Medicine and Montefiore Medical Center, New York, NY, USA.
  • Kim AY; Bluestone Center for Clinical Research, New York University, New York, NY, USA.
  • Lauer G; Department of Oral and Maxillofacial Surgery, New York University, New York, NY, USA.
  • Thomas DL; Massachusetts General Hospital, Boston, MA, USA.
  • Duggal P; Harvard Medical School, Boston, MA, USA.
Genes Immun ; 18(2): 82-87, 2017 03.
Article in En | MEDLINE | ID: mdl-28300059
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 ß=-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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Infections / HIV-1 / Hepatitis C, Chronic / Interleukin-18 / Coinfection Limits: Adult / Female / Humans / Male Language: En Journal: Genes Immun Journal subject: ALERGIA E IMUNOLOGIA / BIOLOGIA MOLECULAR Year: 2017 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Infections / HIV-1 / Hepatitis C, Chronic / Interleukin-18 / Coinfection Limits: Adult / Female / Humans / Male Language: En Journal: Genes Immun Journal subject: ALERGIA E IMUNOLOGIA / BIOLOGIA MOLECULAR Year: 2017 Document type: Article Affiliation country: United States