PMID- 28719954 OWN - NLM STAT- MEDLINE DCOM- 20171117 LR - 20181113 IS - 1738-0006 (Electronic) IS - 0023-4001 (Print) IS - 0023-4001 (Linking) VI - 55 IP - 3 DP - 2017 Jun TI - Subsets of Inflammatory Cytokine Gene Polymorphisms are Associated with Risk of Carcinogenic Liver Fluke Opisthorchis viverrini-Associated Advanced Periductal Fibrosis and Cholangiocarcinoma. PG - 295-304 LID - 10.3347/kjp.2017.55.3.295 [doi] AB - Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF-, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-1beta, IL-6, IFN-gamma, LT-alpha, and TNF-alpha were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-1beta-511C/T, IL-6-174G/C, IFN-gamma +874T/A, LT-alpha +252A/G, and TNF-alpha -308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-alpha +252A/G and TNF-alpha -308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-gamma +874T/A were significantly higher than the variants in CCA cases. IFN-gamma +874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6 -174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA. FAU - Surapaitoon, Arpa AU - Surapaitoon A AD - Biomedical Sciences, Graduate School, Khon Kaen University, Khon Kaen, Thailand. AD - WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Tropical Disease Research Center, Khon Kaen, Thailand. FAU - Suttiprapa, Sutas AU - Suttiprapa S AD - WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Tropical Disease Research Center, Khon Kaen, Thailand. AD - Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Mairiang, Eimorn AU - Mairiang E AD - Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Khuntikeo, Narong AU - Khuntikeo N AD - Liver Fluke and Cholangiocarcinoma Research Center, and Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. FAU - Pairojkul, Chawalit AU - Pairojkul C AD - Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Bethony, Jeffrey AU - Bethony J AD - Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Tropical Diseases of Poverty, School of Medicine & Health Sciences, The George Washington University, Washington DC, 20037, USA. FAU - Brindley, Paul J AU - Brindley PJ AD - Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Tropical Diseases of Poverty, School of Medicine & Health Sciences, The George Washington University, Washington DC, 20037, USA. FAU - Sripa, Banchob AU - Sripa B AD - WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Tropical Disease Research Center, Khon Kaen, Thailand. AD - Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. LA - eng GR - P50 AI098639/AI/NIAID NIH HHS/United States GR - R01 CA164719/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20170630 PL - Korea (South) TA - Korean J Parasitol JT - The Korean journal of parasitology JID - 9435800 RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) SB - IM MH - Adult MH - Aged MH - Animals MH - Bile Duct Neoplasms/*etiology/genetics/*parasitology/pathology MH - Bile Ducts/*pathology MH - Cholangiocarcinoma/*etiology/genetics/*parasitology/pathology MH - Cytokines/*genetics MH - Female MH - Fibrosis MH - *Genetic Association Studies MH - *Genetic Predisposition to Disease MH - Humans MH - *Inflammation Mediators MH - Male MH - Middle Aged MH - Opisthorchiasis/*complications/*parasitology MH - *Opisthorchis MH - Polymorphism, Genetic/*genetics MH - Risk MH - Severity of Illness Index MH - Young Adult PMC - PMC5523895 OTO - NOTNLM OT - Opisthorchis viverrini OT - advanced periductal fibrosis OT - cholangiocarcinoma OT - cytokine gene polymorphisms OT - hepatobiliary disease COIS- CONFLICT OF INTEREST We have no conflict of interest related to this study. EDAT- 2017/07/20 06:00 MHDA- 2017/11/29 06:00 PMCR- 2017/06/01 CRDT- 2017/07/20 06:00 PHST- 2017/04/18 00:00 [received] PHST- 2017/05/08 00:00 [revised] PHST- 2017/05/11 00:00 [accepted] PHST- 2017/07/20 06:00 [entrez] PHST- 2017/07/20 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/06/01 00:00 [pmc-release] AID - kjp-55-3-295 [pii] AID - 10.3347/kjp.2017.55.3.295 [doi] PST - ppublish SO - Korean J Parasitol. 2017 Jun;55(3):295-304. doi: 10.3347/kjp.2017.55.3.295. Epub 2017 Jun 30.