Interactions among Interleukin-6, C-Reactive Protein and Interleukin-6 (-174) G/C Polymorphism in the Pathogenesis of Crohn’s Disease and Ulcerative Colitis

Autor: Boris Takač, Silvio Mihaljević, Ljubica Glavaš-Obrovac, Aleksandar Kibel, Mirjana Suver-Stević, Silvija Canecki-Varžić, Marko Samardžija, Ines Rajkovac, Damir Kovač, Mario Štefanić
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Acta clinica Croatica
Volume 59.
Issue 1.
ISSN: 1333-9451
0353-9466
Popis: Inflammatory bowel diseases are multifactorial disorders the clinical manifestation of which depends on the interaction among immune response, genetic and environmental factors. There is growing evidence that cytokines and gene polymorphisms have an important role in disease pathogenesis in various populations although molecular mechanism of their signaling and interactions is not fully understood yet. The present study aimed at exploring the effects of interleukin-6, C-reactive protein and interleukin-6 rs1800795 polymorphism on the development of Crohn’s disease, ulcerative colitis and inflammatory bowel diseases overall and at determining differences between inflammatory bowel disease patients and healthy controls. A total of 132 inflammatory bowel disease patients and 71 healthy blood donors were investigated. In order to assess the clinical relevance of interleukin-6 and C-reactive protein serum concentration and interleukin-6 rs1800795 single nucleotide polymorphism in patients with Crohn’s disease and ulcerative colitis, we performed a cross-sectional, case-control study. Quantitative assessment of serum interleukin-6 and C-reactive protein was performed with solid-phase, enzyme-labeled, chemiluminescent sequential immunometric and immunoturbidimetric assay, respectively. A real-time fluorescence resonance energy transfer-based method on a LightCyclerTM PCR 1.2 was used for genotyping of IL-6 rs1800795 polymorphism. Both interleukin-6 and C-reactive protein serum levels were elevated in Crohn’s disease and ulcerative colitis patients. Positive correlations were observed between C-reactive protein and interleukin-6 serum concentration and ulcerative colitis activity index as measured by modified Truelove-Witt’s severity index scale. C-reactive protein serum level was higher in Crohn’s disease patients without intestinal resection than in Crohn’s disease patients with prior intestinal resection. In ulcerative colitis patients, interleukin-6 and C-reactive protein serum levels were statistically significantly higher in CC interleukin-6 genotype in comparison to GG+GC genotype. Analysis of the promoter region of the interleukin-6 rs1800795 gene polymorphism showed no statistically significant difference in allele frequency either between inflammatory bowel disease patients and healthy controls or between the two inflammatory bowel disease phenotypes and healthy controls. Associations presented in this study give a potentially important insight into the role of interleukin-6 and C-reactive protein signaling and interleukin-6 polymorphism in the pathogenesis of Crohn’s disease and ulcerative colitis disease.
Upalne bolesti crijeva predstavljaju multifaktorski poremećaj klinička manifestacija kojega ovisi o interakciji imunog odgovora te genetskih i okolišnih čimbenika. Rezultati više novijih istraživanja upućuju na ulogu citokina i polimorfizama gena u patogenezi bolesti u različitim populacijama, iako molekularni mehanizmi njihova singaliziranja i interakcije još nisu dovoljno poznati. Cilj ovoga istraživanja bio je ispitati učinke interleukina-6, C-reaktivnog proteina i interleukin-6 rs1800795 na razvoj Crohnove bolesti, ulceroznoga kolitisa i upalnih bolesti crijeva općenito te utvrditi razlike između skupine ispitanika oboljelih od upalnih bolesti crijeva i kontrolne skupine ispitanika. U istraživanje je uključeno ukupno 132 oboljela od upalnih bolesti crijeva i 71 zdravi davatelj krvi. Serumska koncentracija interleukina-6 određena je kemiluminiscentnom sekvencijskom imunometričnom, a koncentracija C-reaktivnog proteina imunoturbidimetrijskom metodom. Analiza polimorfizma rs1800795 provodila se na uređaju LightCyclerTM PCR 1.2 u stvarnome vremenu temeljem prijenosa energije uslijed fluorescentne rezonancije. Serumske koncentracije interleukina-6 i C-reaktivnoga proteina bile su povišene i u oboljelih od Crohnove bolesti i oboljelih od ulceroznoga kolitisa. Utvrđene su pozitivne korelacije između serumskih koncentracija C-reaktivnoga proteina i interleukina-6 i indeksa aktivnosti ulceroznoga kolitisa mjerenoga prema ljestvici MTWSI. Serumska koncentracija C-reaktivnog proteina bila je viša u oboljelih od Crohnove bolesti bez prethodne resekcije crijeva u usporedbi s oboljelima od Crohnove bolesti s prethodnom resekcijom crijeva. U oboljelih od ulceroznoga kolitisa serumske koncentracije interleukina-6 i C-reaktivnog proteina bile su statistički značajno više kod CC genotipa interleukina-6 u usporedbi s genotipom GG+GC. Analizom polimorfizma promotorske regije IL-6 rs1800795 nisu uočene razlike u učestalosti alela između oboljelih od Crohnove bolelsti, oboljelih od ulceroznoga kolitisa i kontrolne skupine ispitanika, ni razlike između kontrolne skupine ispitanika i oboljelih od upalnih bolesti crijeva općenito. Rezultati ove studije pružaju potencijalno važan uvid u ulogu signaliziranja interleukina-6 i C-reaktivnoga proteina te polimorfizma interleukina-6 u patogenezi Crohnove bolesti i ulceroznoga kolitisa.
Databáze: OpenAIRE
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