Association of polymorphisms in promoter region of TNF-α -238 and -308 with clinical outcomes in patients with immune-mediated inflammatory diseases on anti-TNF therapy.

Autor: Miler M; Department of Clinical Chemistry, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia. marijana.miler@gmail.com., Nikolac Gabaj N; Department of Clinical Chemistry, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia.; Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia., Ćelap I; Department of Clinical Chemistry, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia., Grazio S; Department for Rheumatology, Physical and Rehabilitation Medicine, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia., Tomašić V; Department of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia., Bišćanin A; Department of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia., Mitrović J; Department of Clinical Immunology, Allergology and Rheumatology, Department of Internal Medicine, School of Medicine, University of Zagreb, University Hospital Dubrava, Zagreb, Croatia., Đerek L; Clinical Department of Laboratory Diagnostics, University Hospital Dubrava, Zagreb, Croatia., Morović-Vergles J; Division of Cl Immunology, Allergology and Rheumatology, Department of Internal Medicine, School of Medicine, University of Zagreb, University Hospital Dubrava, Zagreb, Croatia., Vrkić N; Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia., Štefanović M; Department of Clinical Chemistry, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia.; Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
Jazyk: angličtina
Zdroj: Rheumatology international [Rheumatol Int] 2021 Dec; Vol. 41 (12), pp. 2195-2203. Date of Electronic Publication: 2021 Oct 08.
DOI: 10.1007/s00296-021-05016-w
Abstrakt: The hypothesis of the study was that polymorphisms in promoter regions -238 and -308 of TNF-α could be associated with different clinical outcomes in inflammatory bowel diseases (IBD) and immune-mediated rheumatic diseases (IMRD). The aim was to examine the possible association of both polymorphisms with concentration of C-reactive protein (CRP) and fecal calprotectin (fCAL), onset of the remission and development of the ADA in patients on therapy with anti-TNF inhibitors. The prospective study was done in patients with IBD and IMRD on infliximab (IFX) or adalimumab (ADM). Patients were genotyped for TNF-α -238 and -308 polymorphisms. The concentration of CRP, fCAL, IFX or ADM and antibodies to drugs were measured according to manufacturer's instructions and followed-up for 6 or 12 months. Out of all patients (N = 112), number of patients in remission did not differ according to genotypes (for IBD patients P = 0.509 vs 0.223; for IMRD patients P = 0.541 vs 0.132 for TNF-α -238 and -308, respectively). Initial CRP concentration was higher in IBD patients with TNF-α -308 GG than GA/AA genotypes in patients who failed to achieve remission [11.8 (4.4-39.6) vs 3.1 (1.5-6.5), P = 0.033]. In IBD patients with remission, fCAL concentration after at least 6 months of therapy was higher in TNF-α-308 GG than in GA genotype [52 (25-552) vs 20 (20-20) µg/g, P = 0.041]. Our results showed the association of TNF-α -308 GG genotype with a higher concentration of CRP and fecal calprotectin in patients with inflammatory bowel diseases on IFX or ADM therapy. Clinical remission and development of antibodies to anti-TNF drugs were not associated with TNF-α -238 and -308 polymorphisms.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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