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01-12-2021 | Infliximab | Genes and Disease

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

Authors: Marijana Miler, Nora Nikolac Gabaj, Ivana Ćelap, Simeon Grazio, Vedran Tomašić, Alen Bišćanin, Joško Mitrović, Lovorka Đerek, Jadranka Morović-Vergles, Nada Vrkić, Mario Štefanović

Published in: Rheumatology International | Issue 12/2021

Abstract

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.

Blandizzi C, Gionchetti P, Armuzzi A, Caporali R, Chimenti S, Cimaz R et al (2014) The role of tumour necrosis factor in the pathogenesis of immune-mediated diseases. Int J Immunopathol Pharmacol 27(1 Suppl):1–10. https://doi.org/10.1177/03946320140270S101CrossRefPubMed

Kuek A, Hazleman BL, Ostör AJ (2007) Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution. Postgrad Med J 83(978):251–260. https://doi.org/10.1136/pgmj.2006.052688CrossRefPubMedPubMedCentral

Roda G, Jharap B, Neeraj N, Colombel JF (2016) Loss of response to anti-TNFs: definition, epidemiology, and management. Clin Transl Gastroenterol 7(1):e135. https://doi.org/10.1038/ctg.2015.63CrossRefPubMedPubMedCentral

Johnson KJ, Sanchez HN, Schoenbrunner N (2019) Defining response to TNF-inhibitors in rheumatoid arthritis: the negative impact of anti-TNF cycling and the need for a personalized medicine approach to identify primary non-responders. Clin Rheumatol 38(11):2967–2976. https://doi.org/10.1007/s10067-019-04684-1CrossRefPubMed

Aguillón JC, Cruzat A, Aravena O, Salazar L, Llanos C, Cuchacovich M (2006) Could single-nucleotide polymorphisms (SNPs) affecting the tumour necrosis factor promoter be considered as part of rheumatoid arthritis evolution? Immunobiology 211(1–2):75–84. https://doi.org/10.1016/j.imbio.2005.09.005CrossRefPubMed

Burke KE, Khalili H, Garber JJ, Haritunians T, McGovern DPB, Xavier RJ, Ananthakrishnan AN (2018) Genetic markers predict primary nonresponse and durable response to anti-tumor necrosis factor therapy in ulcerative colitis. Inflamm Bowel Dis 24(8):1840–1848. https://doi.org/10.1093/ibd/izy083CrossRefPubMedPubMedCentral

Bek S, Bojesen AB, Nielsen JV, Sode J, Bank S, Vogel U, Andersen V (2017) Systematic review and meta-analysis: pharmacogenetics of anti-TNF treatment response in rheumatoid arthritis. Pharmacogenomics J 17(5):403–411. https://doi.org/10.1038/tpj.2017.26CrossRefPubMedPubMedCentral

Prieto-Pérez R, Cabaleiro T, Daudén E, Abad-Santos F (2013) Gene polymorphisms that can predict response to anti-TNF therapy in patients with psoriasis and related autoimmune diseases. Pharmacogenomics J 13(4):297–305. https://doi.org/10.1038/tpj.2012.53CrossRefPubMed

Lee YH, Ji JD, Bae SC, Song GG (2010) Associations between tumor necrosis factor-α (TNF-α) -308 and -238 G/A polymorphisms and shared epitope status and responsiveness to TNF-α blockers in rheumatoid arthritis: a metaanalysis update. J Rheumatol 37(4):740–746. https://doi.org/10.3899/jrheum.090707CrossRefPubMed

10.

Miceli-Richard C, Comets E, Verstuyft C, Tamouza R, Loiseau P, Ravaud P et al (2008) A single tumour necrosis factor haplotype influences the response to adalimumab in rheumatoid arthritis. Ann Rheum Dis 67(4):478–484. https://doi.org/10.1136/ard.2007.074104CrossRefPubMed

11.

Netz U, Carter JV, Eichenberger MR, Dryden GW, Pan J, Rai SN, Galandiuk S (2017) Genetic polymorphisms predict response to anti-tumor necrosis factor treatment in Crohn’s disease. World J Gastroenterol 23(27):4958–4967. https://doi.org/10.3748/wjg.v23.i27.4958CrossRefPubMedPubMedCentral

12.

Mitrović J, Morović-Vergles J, Martinović Kaliterna D, Anić B, Babić-Naglić Đ, Grazio S et al (2017) 2017 Recommendation proposal of the Croatian Society of rheumatology for the treatment of patients with rheumatoid arthritis with biologic drugs and targeted synthetic drugs. Reumatizam 64(2):65–70 ((in Croatian))

13.

Grazio S, Novak S, Laktašić-Žerjavić N, Anić B, Babić-Naglić Đ, Grubišić F et al (2017) 2017 Recommendation proposal of the Croatian Society of Rheumatology for the treatment of adults with axial spondyloarthritis and psoriatic arthritis with biologic drugs and targated synthetic drugs. Reumatizam 64(2):71–87 ((in Croatian))

14.

Vucelić B, Čuković-Čavka S, Banić M, Bilić A, Borzan V, Duvnjak M et al (2013) Croatian consensus on the treatment of inflammatory bowel diseases with biologic therapy. Acta Med Croatica 67(2):75–86PubMed

15.

Gomollón F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO et al (2017) ECCO. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: Part 1: Diagnosis and medical management. J Crohns Colitis 11(1):3–25. https://doi.org/10.1093/ecco-jcc/jjw168CrossRefPubMed

16.

Torres J, Bonovas S, Doherty G, Kucharzik T, Gisbert JP, Raine T et al (2020) ECCO guidelines on therapeutics in Crohn’s Disease: medical treatment. J Crohns Colitis 14(1):4–22. https://doi.org/10.1093/ecco-jcc/jjz180CrossRefPubMed

17.

Lin X, Qiu Y, Feng R, Chen B, He Y, Zeng Z, Zhang S, Chen M, Mao R (2020) Normalization of C-reactive protein predicts better outcome in patients with Crohn’s disease with mucosal healing and deep remission. Clin Transl Gastroenterol. https://doi.org/10.14309/ctg.0000000000000135CrossRefPubMedPubMedCentral

18.

Zaghlol HM, Abdelshafy S, Mohamed RA, Abdelaleem EA (2019) Tumour necrosis factor gene polymorphisms in Egyptian patients with rheumatoid arthritis and their relation to disease activity and severity. Cent Eur J Immunol 44(3):277–284. https://doi.org/10.5114/ceji.2019.89602CrossRefPubMedPubMedCentral

19.

Gheita TA, Azkalany GS, Gaber W, Mohey A (2015) Clinical significance of serum TNFα and -308 G/A promoter polymorphism in rheumatoid arthritis. Egypt Rheumatol 37(2):49–54. https://doi.org/10.1016/j.ejr.2014.07.001CrossRef

20.

Orr CK, Najm A, Young F, McGarry T, Biniecka M, Fearon U, Veale DJ (2018) The utility and limitations of CRP, ESR and DAS28-CRP in appraising disease activity in rheumatoid arthritis. Front Med (Lausanne) 5:185. https://doi.org/10.3389/fmed.2018.00185CrossRef

21.

Chang S, Malter L, Hudesman D (2015) Disease monitoring in inflammatory bowel disease. World J Gastroenterol 21(40):11246–11259. https://doi.org/10.3748/wjg.v21.i40.11246CrossRefPubMedPubMedCentral

22.

Sun MH, Sun LQ, Guo GL, Zhang S (2019) Tumour necrosis factor-α gene -308 G > A and -238 G > A polymorphisms are associated with susceptibility to irritable bowel syndrome and drug efficacy in children. J Clin Pharm Ther 44(2):180–187. https://doi.org/10.1111/jcpt.12775CrossRefPubMed

23.

Sashio H, Tamura K, Ito R, Yamamoto Y, Bamba H, Kosaka T et al (2002) Polymorphisms of the TNF gene and the TNF receptor superfamily member 1B gene are associated with susceptibility to ulcerative colitis and Crohn’s disease, respectively. Immunogenetics 53(12):1020–1027. https://doi.org/10.1007/s00251-001-0423-7CrossRefPubMed

24.

Bouma G, Crusius JB, Garcia-Gonzalez MA, Meijer BU, Hellemans HP, Hakvoort RJ et al (1999) Genetic markers in clinically well defined patients with ulcerative colitis (UC). Clin Exp Immunol 115:294–300. https://doi.org/10.1046/j.1365-2249.1999.00797.xCrossRefPubMedPubMedCentral

25.

Matsuoka K, Hamada S, Shimizu M, Nanki K, Mizuno S, Kiyohara H et al (2018) Factors predicting the therapeutic response to infliximab during maintenance therapy in Japanese patients with Crohn’s disease. PLoS ONE 13(10):e0204632. https://doi.org/10.1371/journal.pone.0204632CrossRefPubMedPubMedCentral

26.

Song GG, Seo YH, Kim JH, Choi SJ, Ji JD, Lee YH (2015) Association between TNF-α (-308 A/G, -238 A/G, -857 C/T) polymorphisms and responsiveness to TNF-α blockers in spondyloarthropathy, psoriasis and Crohn’s disease: a meta-analysis. Pharmacogenomics 16(12):1427–1437. https://doi.org/10.2217/pgs.15.90CrossRefPubMed

27.

Pallio G, Mannino F, Irrera N, Eid AH, Squadrito F, Bitto A (2020) Polymorphisms involved in response to biological agents used in rheumatoid arthritis. Biomolecules 10(9):1203. https://doi.org/10.3390/biom10091203CrossRefPubMedCentral

28.

Barber GE, Yajnik V, Khalili H, Giallourakis C, Garber J, Xavier R, Ananthakrishnan AN (2016) Genetic markers predict primary non-response and durable response to anti-TNF biologic therapies in Crohn’s disease. Am J Gastroenterol 111(12):1816–1822. https://doi.org/10.1038/ajg.2016.408CrossRefPubMedPubMedCentral

29.

Massey J, Plant D, Hyrich K, Morgan AW, Wilson AG, Spiliopoulou A, Colombo M, McKeigue P, Isaacs J, Cordell H, Pitzalis C, Barton A, BRAGGSS, MATURA Consortium (2018) Genome-wide association study of response to tumour necrosis factor inhibitor therapy in rheumatoid arthritis. Pharmacogenomics J 18(5):657–664. https://doi.org/10.1038/s41397-018-0040-6CrossRefPubMedPubMedCentral

30.

Steenholdt C, Al-khalaf M, Brynskov J, Bendtzen K, Thomsen OØ, Ainsworth MA (2012) Clinical implications of variations in anti-infliximab antibody levels in patients with inflammatory bowel disease. Inflamm Bowel Dis 18(12):2209–2217. https://doi.org/10.1002/ibd.22910CrossRefPubMed

31.

Louis E, Vermeire S, Rutgeerts P, De Vos M, Van Gossum A, Pescatore P, Fiasse R, Pelckmans P, Reynaert H, D’Haens G, Malaise M, Belaiche J (2002) A positive response to infliximab in Crohn disease: association with a higher systemic inflammation before treatment but not with -308 TNF gene polymorphism. Scand J Gastroenterol 37(7):818–824CrossRef

32.

Hadinedoushan H, Noorbakhsh P, Soleymani-Salehabadi H (2016) Tumor necrosis factor alpha gene polymorphism and association with its serum level in Iranian population with rheumatoid arthritis. Arch Rheumatol 31(4):306–313. https://doi.org/10.5606/ArchRheumatol.2016.5907CrossRefPubMedPubMedCentral

33.

Avdagić N, Babić N, Šeremet M, Delić-Šarac M, Drače Z, Denjalić A, Nakaš-Ićindić E (2013) Tumor necrosis factor-alpha serum level in assessment of disease activity in inflammatory bowel diseases. Med Glas (Zenica) 10(2):211–216

34.

De Santis IP, Lindenau JD-R, Ramos RB, Silva TR, Casanova G, Oppermann K, Spritzer PM (2020) C-reactive protein gene rs1205 polymorphism is associated with low-grade chronic inflammation in postmenopausal women. Women Midlife Health. https://doi.org/10.1186/s40695-020-00051-2CrossRef

35.

Polterauer S, Grimm C, Zeillinger R, Heinze G, Tempfer C, Reinthaller A, Hefler L (2011) Association of C-reactive protein (CRP) gene polymorphisms, serum CRP levels and cervical cancer prognosis. Anticancer Res 31(6):2259–2264PubMed

36.

Martínez-Calatrava MJ, González-Sánchez JL, Martínez-Larrad MT, Pérez-Barba M, Serrano-Ríos M (2007) Common haplotypes of the C-reactive protein gene and circulating leptin levels influence the interindividual variability in serum C-reactive protein levels. J Thromb Haemost 98(11):1088–1095. https://doi.org/10.1160/th07-03-0231CrossRef

37.

Hassani M, Dehani M, Zare Rafie M, Esmaeilzadeh E, Davar S, Pakzad B, Mosallaei M, Hoseini SM, Bayat H, Soosanabadi M (2021) Investigation of rs531564 polymorphism in the primary microRNA-124 gene in patients with systemic lupus erythematosus and rheumatoid arthritis: association with disease susceptibility and clinical characteristics. Iran J Allergy Asthma Immunol 20(3):303–313. https://doi.org/10.18502/ijaai.v20i3.6336CrossRefPubMed

38.

Miler M, Nikolac Gabaj N, Grazio S, Vahtarić A, Vrtarić A, Grubišić F et al (2020) Lower concentration of vitamin D is associated with lower DAS28 and VAS-pain scores in patients with inflammatory rheumatic diseases treated with infliximab: a pilot study. Rheumatol Int 40(9):1455–1461. https://doi.org/10.1007/s00296-020-04607-3CrossRefPubMed

39.

Chen P, Zhou G, Lin J, Li L, Zeng Z, Chen M, Zhang S (2020) Serum biomarkers for inflammatory bowel disease. Front Med (Lausanne) 7:123. https://doi.org/10.3389/fmed.2020.00123CrossRef

Title: 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
Authors: Marijana Miler
Nora Nikolac Gabaj
Ivana Ćelap
Simeon Grazio
Vedran Tomašić
Alen Bišćanin
Joško Mitrović
Lovorka Đerek
Jadranka Morović-Vergles
Nada Vrkić
Mario Štefanović
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Keywords: Infliximab
Chronic Inflammatory Bowel Disease
Adalimumab
Rheumatoid Arthritis
Published in: Rheumatology International / Issue 12/2021
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-021-05016-w

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