{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:26:04Z","timestamp":1787574364254,"version":"build-2736575974"},"reference-count":62,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-66\/2024-03\/200110"],"award-info":[{"award-number":["451-03-66\/2024-03\/200110"]}]},{"award":["451-03-66\/2024-03\/200110"],"award-info":[{"award-number":["451-03-66\/2024-03\/200110"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Respiratory Society of Serbia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Progressive pulmonary fibrosis (PPF) comprises interstitial lung diseases characterized by progressive fibrosis and lung function decline. Nintedanib slows disease progression by inhibiting FGFR, VEGFR, and PDGFR signaling, but treatment response varies among patients. We investigated whether VEGFR2, PDGFRB, and TGFB1 gene variants are associated with nintedanib treatment outcomes, including changes in pulmonary function, diffusing capacity and adverse effects. This prospective study included 75 patients with PPF diagnosed according to ATS\/ERS\/JRS\/ALAT criteria and treated with nintedanib at the Clinic of Pulmonology, University Clinical Center of Serbia. Spirometry and diffusing capacity were assessed at baseline and after 6 and 12 months. Genotyping of VEGFR2 rs2071559 and rs1870377; PDGFRB rs2302273, rs2229562, and rs246395; and TGFB1 rs1800470 was performed using TaqMan\u00ae assays. Carriers of the PDGFRB rs2302273 A allele more frequently experienced gastrointestinal adverse events (45.2% vs. 20.5%; p = 0.022; OR 3.2, 95% CI 1.156\u20138.866) and diarrhea (38.7% vs. 15.9%; p = 0.026; OR 3.3, 95% CI 1.129\u20139.869). Patients with the PDGFRB rs246395 TT genotype more frequently had a \u226515% decline in DLCO after one year (46% vs. 22%; p = 0.038; OR 3.0, 95% CI 1.045\u20138.394). No significant associations were observed for the analyzed VEGFR2 or TGFB1 variants. These findings suggest that PDGFRB variants may be associated with nintedanib treatment outcomes, although confirmation in larger cohorts is needed.<\/jats:p>","DOI":"10.3390\/ijms27177546","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:19Z","timestamp":1787572039000},"page":"7546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of PDGFRB, VEGFR2, and TGFB1 Gene Polymorphisms with Nintedanib Efficacy and Adverse Effects in Patients with Progressive Pulmonary Fibrosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0825-4748","authenticated-orcid":false,"given":"Natasa","family":"Djurdjevic","sequence":"first","affiliation":[{"name":"Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3564-2623","authenticated-orcid":false,"given":"Marija Dusanovi\u0107","family":"Pjevic","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1787-1438","authenticated-orcid":false,"given":"Mihailo","family":"Stjepanovic","sequence":"additional","affiliation":[{"name":"Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6516-1970","authenticated-orcid":false,"given":"Nikola","family":"Colic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Centre for Radiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9989-3862","authenticated-orcid":false,"given":"Sanja","family":"Dimic-Janjic","sequence":"additional","affiliation":[{"name":"Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8529-8624","authenticated-orcid":false,"given":"Jelena","family":"Jankovic","sequence":"additional","affiliation":[{"name":"Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1103-5669","authenticated-orcid":false,"given":"Nikola","family":"Maric","sequence":"additional","affiliation":[{"name":"Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrej","family":"Zecevic","sequence":"additional","affiliation":[{"name":"Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6837-5222","authenticated-orcid":false,"given":"Milica","family":"Terzic","sequence":"additional","affiliation":[{"name":"Clinic for Allergology and Immunology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2848-6521","authenticated-orcid":false,"given":"Aleksa","family":"Golubovic","sequence":"additional","affiliation":[{"name":"Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3289-8148","authenticated-orcid":false,"given":"Ivan","family":"Milivojevic","sequence":"additional","affiliation":[{"name":"Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6489-5187","authenticated-orcid":false,"given":"Maja","family":"Omcikus","sequence":"additional","affiliation":[{"name":"Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9350-2461","authenticated-orcid":false,"given":"Branislav","family":"Ilic","sequence":"additional","affiliation":[{"name":"Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4861-4189","authenticated-orcid":false,"given":"Katarina","family":"Lukic","sequence":"additional","affiliation":[{"name":"Centre for Radiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1807-4571","authenticated-orcid":false,"given":"Snjezana","family":"Mijatovic","sequence":"additional","affiliation":[{"name":"Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, 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disease","volume":"44","author":"Nishioka","year":"2024","journal-title":"Inflamm. Regen."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Nagy, A., Nagy, T., Kolonics-Farkas, A.M., Eszes, N., Vincze, K., Barczi, E., Tarnoki, A.D., Tarnoki, D.L., Nagy, G., and Kiss, E. (2021). Autoimmune progressive fibrosing interstitial lung disease: Predictors of fast decline. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.778649"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"L600","DOI":"10.1152\/ajplung.00310.2021","article-title":"From pulmonary fibrosis to progressive pulmonary fibrosis: A lethal pathobiological jump","volume":"321","author":"Selman","year":"2021","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s12931-021-01749-1","article-title":"Estimates of epidemiology, mortality and disease burden associated with progressive fibrosing interstitial lung disease in France: The PROGRESS study","volume":"22","author":"Nasser","year":"2021","journal-title":"Respir. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1080\/03007995.2019.1647040","article-title":"Progressive fibrosing interstitial lung diseases: Current practice in diagnosis and management","volume":"35","author":"Wijsenbeek","year":"2019","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4100","DOI":"10.1007\/s12325-021-01786-8","article-title":"Prevalence and incidence of chronic fibrosing interstitial lung diseases with a progressive phenotype in the United States estimated in a large claims database analysis","volume":"38","author":"Olson","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1136\/annrheumdis-2020-217230","article-title":"Mechanisms of progressive fibrosis in connective tissue disease-associated interstitial lung diseases","volume":"80","author":"Spagnolo","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Althobiani, M.A., Russell, A.M., Jacob, J., Ranjan, Y., Folarin, A.A., Hurst, J.R., and Porter, J.C. (2024). Interstitial lung disease: A review of classification, etiology, epidemiology, clinical diagnosis, pharmacological and non-pharmacological treatment. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1296890"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kim, Y., Yang, H.I., and Kim, K.S. (2023). Etiology and pathogenesis of rheumatoid arthritis-interstitial lung disease. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202309.0235.v1"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"La Rocca, G., Ferro, F., Sambataro, G., Elefante, E., Fonzetti, S., Fulvio, G., Navarro, I.C., Mosca, M., and Baldini, C. (2023). Primary Sj\u00f6gren\u2019s syndrome-related interstitial lung disease: A clinical review discussing current controversies. J. Clin. Med., 12.","DOI":"10.3390\/jcm12103428"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/mi.2008.85","article-title":"Pulmonary fibrosis: Pathogenesis, etiology and regulation","volume":"2","author":"Wilson","year":"2009","journal-title":"Mucosal Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15073","DOI":"10.1038\/s41598-023-41294-z","article-title":"Optimal controlling of anti-TGF-\u03b2 and anti-PDGF medicines for preventing pulmonary fibrosis","volume":"13","author":"Malek","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s12931-014-0157-3","article-title":"Anti-fibrotic effects of nintedanib in lung fibroblasts derived from patients with idiopathic pulmonary fibrosis","volume":"15","author":"Hostettler","year":"2014","journal-title":"Respir. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hall, J.K., Bates, J.H.T., Krishnan, R., Kim, J.H., Deng, Y., Lutchen, K.R., and Suki, B. (2024). Elucidating the interaction between stretch and stiffness using an agent-based spring network model of progressive pulmonary fibrosis. Front. Netw. Physiol., 4.","DOI":"10.3389\/fnetp.2024.1396383"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.matbio.2013.11.002","article-title":"Extracellular matrix proteins: A positive feedback loop in lung fibrosis?","volume":"34","author":"Blaauboer","year":"2014","journal-title":"Matrix Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1172\/JCI71386","article-title":"Fibrotic extracellular matrix activates a profibrotic positive feedback loop","volume":"124","author":"Parker","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.amjms.2026.02.015","article-title":"Incidence and prevalence of progressive pulmonary fibrosis (PPF): A systematic literature review and meta-analysis","volume":"371","author":"Golchin","year":"2026","journal-title":"Am. J. Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"152500","DOI":"10.1016\/j.semarthrit.2024.152500","article-title":"Efficacy and safety of pharmacological treatments for auto-immune disease-associated interstitial lung disease: A systematic review and network meta-analysis","volume":"68","author":"Weng","year":"2024","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"00423-2022","DOI":"10.1183\/23120541.00423-2022","article-title":"Nintedanib for non-IPF progressive pulmonary fibrosis: 12-month outcome data from a real-world multicentre observational study","volume":"9","author":"Raman","year":"2023","journal-title":"ERJ Open Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1900161","DOI":"10.1183\/13993003.00161-2019","article-title":"Potential of nintedanib in treatment of progressive fibrosing interstitial lung diseases","volume":"54","author":"Wollin","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s40265-021-01487-0","article-title":"Nintedanib: A review in fibrotic interstitial lung diseases","volume":"81","author":"Lamb","year":"2021","journal-title":"Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ruaro, B., Gandin, I., Pozzan, R., Tavano, S., Bozzi, C., Hughes, M., Kodric, M., Cifaldi, R., Lerda, S., and Confalonieri, M. (2023). Nintedanib in idiopathic pulmonary fibrosis: Tolerability and safety in a real-life experience in a single centre in patients also treated with oral anticoagulant therapy. Pharmaceuticals, 16.","DOI":"10.3390\/ph16020307"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Piecuch, D., Hanczyk, E., Zemsta, K., Zwoli\u0144ski, M., Kopcia\u0142, S., and Jo\u0144ska, J. (2025). Diagnostics, efficacy, and safety of immunomodulatory and anti-fibrotic treatment for interstitial lung disease associated with systemic scleroderma. Diagnostics, 15.","DOI":"10.3390\/diagnostics15172243"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e70371","DOI":"10.1111\/cts.70371","article-title":"Risk and association of specific HLA alleles with nintedanib-induced gastrointestinal adverse reactions: A discovery study in an Italian population","volume":"18","author":"Mocci","year":"2025","journal-title":"Clin. Transl. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"17534666211042529","DOI":"10.1177\/17534666211042529","article-title":"DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: A pilot study","volume":"15","author":"Doubkova","year":"2021","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lewandowska, K.B., Lechowicz, U., Ro\u017cy, A., Falis, M., B\u0142asi\u0144ska, K., Jakubowska, L., Franczuk, M., \u017bo\u0142nowska, B., Gryczka-Wr\u00f3bel, J., and Radwan-Rohrenschef, P. (2025). MUC5B polymorphism in patients with idiopathic pulmonary fibrosis\u2014Does it really matter?. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26052218"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1021\/jm501562a","article-title":"Nintedanib: From discovery to the clinic","volume":"58","author":"Roth","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1056\/NEJMoa1402584","article-title":"Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis","volume":"370","author":"Richeldi","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1056\/NEJMoa1103690","article-title":"Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis","volume":"365","author":"Richeldi","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1124\/jpet.113.208223","article-title":"Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis","volume":"349","author":"Wollin","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1056\/NEJMoa1903076","article-title":"Nintedanib for systemic sclero-sis-associated interstitial lung disease","volume":"380","author":"Distler","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Khedoe, P., Marges, E., Hiemstra, P., Ninaber, M., and Geelhoed, M. (2020). Interstitial lung disease in patients with systemic sclerosis: Toward personalized-medicine-based prediction and drug screening models of systemic sclerosis-related interstitial lung disease. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01990"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1513\/AnnalsATS.202103-343OC","article-title":"Nintedanib in progressive pulmonary fibrosis: A systematic review and meta-analysis","volume":"19","author":"Ghazipura","year":"2022","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27115","DOI":"10.1038\/s41598-025-12952-1","article-title":"Circulating biomarkers in patients with progressive fibrosing interstitial lung disease treated with nintedanib: A pilot study","volume":"15","author":"Miceli","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"00558","DOI":"10.1183\/23120541.00558-2023","article-title":"Effects of nintedanib on circulating biomarkers of idiopathic pulmonary fibrosis","volume":"10","author":"Jenkins","year":"2024","journal-title":"ERJ Open Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Andrisano, A.G., Castaldo, N., Giuliana, F., Femia, D., Morana, G., Patruno, V., Monteleone, G., Reccardini, N., Cifaldi, R., and Hughes, M. (2025). Retrospective observational study of nintedanib in managing idiopathic and progressive pulmonary fibrosis in routine practice. J. Clin. Med., 14.","DOI":"10.3390\/jcm14186665"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1097\/MCP.0000000000000289","article-title":"Pharmacogenetics and interstitial lung disease","volume":"22","author":"Oldham","year":"2016","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"177","DOI":"10.5114\/reum.2016.62472","article-title":"Personalized medicine in rheumatology","volume":"54","author":"Kwiatkowska","year":"2016","journal-title":"Reumatologia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1111\/cas.13071","article-title":"FGFR gene alterations in lung squamous cell carcinoma are potential targets for the multikinase inhibitor nintedanib","volume":"107","author":"Hibi","year":"2016","journal-title":"Cancer Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/tpj.2014.40","article-title":"Genes involved in pericyte-driven tumor maturation predict treatment benefit of first-line FOLFIRI plus bevacizumab in patients with metastatic colorectal cancer","volume":"15","author":"Volz","year":"2015","journal-title":"Pharmacogenomics J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/nar\/29.1.308","article-title":"dbSNP: The NCBI database of genetic vari-ation","volume":"29","author":"Sherry","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Oelschlaeger, P. (2024). Molecular mechanisms and the significance of synonymous mutations. Biomolecules, 14.","DOI":"10.3390\/biom14010132"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12062","DOI":"10.1038\/s41598-019-48593-4","article-title":"Gastrointestinal adverse effects of nintedanib and the associated risk factors in patients with idiopathic pulmonary fibrosis","volume":"9","author":"Kato","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/bph.12452","article-title":"PDGF and TGF-\u03b2 promote tenascin-C expression in subepithelial myofibroblasts and contribute to intestinal mucosal protection in mice","volume":"171","author":"Islam","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e679","DOI":"10.1016\/S2665-9913(22)00193-X","article-title":"Safety and tolerability of nintedanib in patients with interstitial lung diseases in subgroups by sex: A post-hoc analysis of pooled data from four randomised controlled trials","volume":"4","author":"Volkmann","year":"2022","journal-title":"Lancet Rheumatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10908","DOI":"10.21037\/jtd-2025-130","article-title":"Adverse side-effects of antifibrotic drugs and outcome of treatment in idiopathic pulmonary fibrosis","volume":"17","author":"Jovanovic","year":"2025","journal-title":"J. Thorac. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1507\/endocrj.EJ19-0480","article-title":"Gene polymorphisms of VEGF and VEGFR2 are associated with the severity of Hashimoto\u2019s disease and the intractability of Graves\u2019 disease, respectively","volume":"67","author":"Okamoto","year":"2020","journal-title":"Endocr. J."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Marin, J.J.G., Serrano, M.A., Monte, M.J., Sanchez-Martin, A., Temprano, A.G., Briz, O., and Romero, M.R. (2020). Role of genetic variations in the hepatic handling of drugs. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082884"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.3892\/ol.2020.11857","article-title":"Clinical outcomes and safety of apatinib monotherapy in the treatment of patients with advanced epithelial ovarian carcinoma who progressed after standard regimens and the analysis of the VEGFR2 polymorphism","volume":"20","author":"Yan","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"37599","DOI":"10.18632\/oncotarget.9229","article-title":"Angiogenesis genotyping in the selection of first-line treatment with either sunitinib or pazopanib for advanced renal cell carcinoma","volume":"7","author":"Bianconi","year":"2016","journal-title":"Oncotarget"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.clgc.2015.02.007","article-title":"Genotype correlations with blood pressure and efficacy from a randomized phase III trial of second-line axitinib versus sorafenib in metastatic renal cell carcinoma","volume":"13","author":"Escudier","year":"2015","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s12032-014-0209-z","article-title":"The relationship of kinase insert domain receptor gene polymorphisms and clinical outcome in advanced hepatocellular carcinoma patients treated with sorafenib","volume":"31","author":"Zheng","year":"2014","journal-title":"Med. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1002\/ijc.28772","article-title":"VEGF and VEGFR genotyping in the prediction of clinical outcome for HCC patients receiving sorafenib: The ALICE-1 study","volume":"135","author":"Scartozzi","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1158\/1078-0432.CCR-18-1724","article-title":"Phase III trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma: Exploratory pharmacogenomic analysis","volume":"25","author":"George","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/S1470-2045(11)70266-2","article-title":"Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: A multicentre, observational, prospective study","volume":"12","author":"Esteban","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Estevez-Garcia, P., Casta\u00f1o, A., Martin, A.C., Lopez-Rios, F., Iglesias, J., Mu\u00f1oz-Galv\u00e1n, S., Lopez-Calderero, I., Molina-Pinelo, S., Pastor, M.D., and Carnero, A. (2012). PDGFR\u03b1\/\u03b2 and VEGFR2 polymorphisms in colorectal cancer: Incidence and implications in clinical outcome. BMC Cancer, 12.","DOI":"10.1186\/1471-2407-12-514"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"E18","DOI":"10.1164\/rccm.202202-0399ST","article-title":"Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS\/ERS\/JRS\/ALAT Clinical Practice Guideline","volume":"205","author":"Raghu","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/nar\/16.3.1215","article-title":"A simple salting out procedure for extracting DNA from human nucleated cells","volume":"16","author":"Miller","year":"1988","journal-title":"Nucleic Acids Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.jacc.2007.04.074","article-title":"Polymorphisms of KDR gene are associated with coronary heart disease","volume":"50","author":"Wang","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2901","DOI":"10.1007\/s10620-012-2238-9","article-title":"Transforming growth factor beta1 gene variation Leu10Pro affects secretion and function in hepatic cells","volume":"57","author":"Gu","year":"2012","journal-title":"Dig. Dis. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/bioinformatics\/bth457","article-title":"Haploview: Analysis and visualization of LD and haplotype maps","volume":"21","author":"Barrett","year":"2005","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7546\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:55:22Z","timestamp":1787572522000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,23]]},"references-count":62,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177546"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177546","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,23]]}}}