Vergara, CandelariaThio, ChloeLatanich, RachelCox, Andrea L.Kirk, Gregory D.Mehta, Shruti H.Busch, MichaelMurphy, Edward LVillacres, Maria C.Peters, Marion G.French, Audrey L.Golub, ElizabethEron, JosephLahiri, Cecile DelilleShrestha, SadeepGustafson, DeborahYoung, MaryAnastos, KathrynAouizerat, BradleyKim, ArthurLauer, GeorgThomas, David L.Duggal, Priya2017-12-052016Vergara, 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.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34491999Inflammasomes 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.en-USJournal Article2017-12-0510.1038/gene.2017.2