{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:34:57Z","timestamp":1791293697849,"version":"4.1.0"},"reference-count":68,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III","award":["PT13\/0010\/0039"],"award-info":[{"award-number":["PT13\/0010\/0039"]}]},{"name":"Biobank of the Hospital Universitario Virgen de las Nieves","award":["PT13\/0010\/0039"],"award-info":[{"award-number":["PT13\/0010\/0039"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06\u201330.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24\u201314.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04\u20131.18), FCER1B rs569108-AA (p &lt; 0.001; OR = 171.06; 95% CI = 12.94\u20136264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71\u201376.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 \u00d7 108; 95% CI = 1.8 \u00d7 10\u221219\u2013NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19\u2013269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05\u201316.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22\u201320.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58\u201391.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7\u201375.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9\u2013112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16\u201373.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.<\/jats:p>","DOI":"10.3390\/ijms25158139","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T06:17:44Z","timestamp":1721974664000},"page":"8139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["SingleNucleotide Polymorphisms as Biomarkers of Mepolizumab and Benralizumab Treatment Response in Severe Eosinophilic Asthma"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6930-8933","authenticated-orcid":false,"given":"Susana","family":"Rojo-Tolosa","sequence":"first","affiliation":[{"name":"Respiratory Medicine Department, University Hospital Virgen de las Nieves, 18014 Granada, Spain"},{"name":"Pharmacy Service, Pharmacogenetics Unit, University Hospital Virgen de las Nieves, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8076-956X","authenticated-orcid":false,"given":"Jos\u00e9 Antonio","family":"S\u00e1nchez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Respiratory Medicine Department, University Hospital Virgen de las Nieves, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Caballero-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Respiratory Medicine Department, University Hospital Virgen de las Nieves, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5111-3895","authenticated-orcid":false,"given":"Laura Elena","family":"Pineda-Lancheros","sequence":"additional","affiliation":[{"name":"Pharmacy Service, Pharmacogenetics Unit, University Hospital Virgen de las Nieves, 18014 Granada, Spain"},{"name":"Department of Pharmacy, Faculty of Sciences, National University of Colombia, Bogota Campus, Cra. 30 No. 45-03, Bogot\u00e1 11001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Victoria","family":"Gonz\u00e1lez-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Respiratory Medicine Department, University Hospital Virgen de las Nieves, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"P\u00e9rez-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Center of Biomedical Research, Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology \u201cJos\u00e9 Mataix\u201d, University of Granada, Avda. del Conocimiento s\/n., 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Jim\u00e9nez-Morales","sequence":"additional","affiliation":[{"name":"Pharmacy Service, Pharmacogenetics Unit, University Hospital Virgen de las Nieves, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n","family":"Morales-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Respiratory Medicine Department, University Hospital Virgen de las Nieves, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"ref_1","unstructured":"Sociedad Espa\u00f1ola de Neumolog\u00eda y Cirug\u00eda Tor\u00e1cica (2024, April 03). 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