Subsets of Inflammatory Cytokine Gene Polymorphisms are Associated with Risk of Carcinogenic Liver Fluke Opisthorchis viverrini-Associated Advanced Periductal Fibrosis and Cholangiocarcinoma

Arpa Surapaitoon; Sutas Suttiprapa; Eimorn Mairiang; Narong Khuntikeo; Chawalit Pairojkul; Jeffrey Bethony; Paul J. Brindley; Banchob Sripa

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저자정보: Arpa Surapaitoon (Khon Kaen University) Sutas Suttiprapa (Tropical Disease Research Center) Eimorn Mairiang (Khon Kaen University) Narong Khuntikeo (Khon Kaen University) Chawalit Pairojkul (Department of Pathology) Jeffrey Bethony (The George Washington University) Paul J. Brindley (The George Washington University) Banchob Sripa (Tropical Disease Research Center)

저널정보: 대한기생충학열대의학회 Parasites, Hosts and Diseases The Korean Journal of Parasitology Vol.55 No.3

발행연도: 2017.6

수록면: 295 - 304 (10page)

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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-1β, IL-6, IFN-γ, LT-α, and TNF-α were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-1β -511C/T, IL-6 -174G/C, IFN-γ +874T/A, LT-α +252A/G, and TNF-α -308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-α +252A/G and TNF-α -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-γ +874T/A were significantly higher than the variants in CCA cases. IFN-γ +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.

#Opisthorchis viverrini #hepatobiliary disease #advanced periductal fibrosis #cholangiocarcinoma #cytokine gene polymorphisms

참고문헌 (37)

참고문헌 신청

[학술지(정기간행물)] - Sripa B / 2012 / The tumorigenic liver fluke Opisthorchis viverrini-multiple pathways to cancer / Trends Parasitol 28 : 395 ~ 407

[학술지(정기간행물)] - Sripa B / 2007 / Liver fluke induces cholangiocarcinoma / PLoS Med 4 : e201 ~

[학술지(정기간행물)] - Mairiang E / 2006 / Ultrasound screening for Opisthorchis viverrini-associated cholangiocarcinomas : experience in an endemic area / Asian Pac J Cancer Prev 7 : 431 ~ 433

[학술지(정기간행물)] - Mairiang E / 2012 / Ultrasonography assessment of hepatobiliary abnormalities in 3359 subjects with Opisthorchis viverrini infection in endemic areas of Thailand / Parasitol Int 61 : 208 ~ 211

[학술지(정기간행물)] - Bradley JR / 2008 / TNF-mediated inflammatory disease / J Pathol 214 : 149 ~ 160

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