{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:51:46Z","timestamp":1791597106956,"version":"4.3.4"},"reference-count":40,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017638","name":"Ministry of Health of the Russian Federation","doi-asserted-by":"publisher","award":["1025101700003-6"],"award-info":[{"award-number":["1025101700003-6"]}],"id":[{"id":"10.13039\/501100017638","id-type":"DOI","asserted-by":"publisher"}]},{"award":["1025101700003-6"],"award-info":[{"award-number":["1025101700003-6"]}],"id":[{"id":"https:\/\/ror.org\/01p8ehb87","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Genetic determinants of response to biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA) remain insufficiently characterized. We developed a targeted sequencing panel of candidate immunogenetic variants identified through a literature review and evaluated associations with response to TNF-\u03b1 inhibitors, response to IL-6 inhibitors, and difficult-to-treat RA (D2TRA). Whole-blood DNA was sequenced using custom hybridization capture on a DNBSEQ-G400 platform (2 \u00d7 150 bp). Reads were aligned to hg38 using BWA-MEM, and variants were called with GATK HaplotypeCaller. After quality control, the D2TRA analysis included 154 patients (59 D2TRA and 95 non-D2TRA); drug-response analyses included 66 anti-TNF patients (26 responders, 40 non-responders) and 69 anti-IL-6 patients (29 responders, 40 non-responders). Treatment-response associations were assessed using unadjusted allelic chi-square tests with multiple-testing correction; D2TRA was analyzed using logistic regression adjusted for age, sex, and body mass index. For IL-6 inhibitor response, rs11656130\/MAP2K6 (p = 0.0163; FDR = 0.3704) and rs4910008\/GALNT18 (p = 0.0212; FDR = 0.3704) were identified, while rs7767069\/LINC02549 was associated with TNF-\u03b1 inhibitor response (p = 0.0171; FDR = 0.5968). For D2TRA, rs1813443 in CNTN5 (OR = 1.85, p = 0.017) and rs12081765, an intergenic variant near LMX1A\/RXRG (OR = 0.59, p = 0.028), were nominally associated; neither association remained significant after multiple-testing correction. With the current sample sizes, the study could detect only large genetic effects, and was underpowered for these after Bonferroni correction (\u03b1 = 0.00143). The findings highlight the limited reproducibility of candidate pharmacogenetic markers in RA and provide a targeted panel and analytical framework for larger replication studies.<\/jats:p>","DOI":"10.3390\/ijms27198800","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:25:44Z","timestamp":1790850344000},"page":"8800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Sequencing-Based Re-Evaluation of Candidate Immunogenetic Variants for Biologic Treatment Response and Difficult-to-Treat Rheumatoid Arthritis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3235-1425","authenticated-orcid":false,"given":"Alena I.","family":"Zagrebneva","sequence":"first","affiliation":[{"name":"Organizational and Methodological Department, North-Western State Medical University Named After I.I. Mechnikov, 41, Kirochnaya St., Saint Petersburg 191015, Russia"},{"name":"Moscow Clinical Research Center \u201cHospital No. 52\u201d, 3, Pekhotnaya St., Moscow 123182, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena N.","family":"Simonova","sequence":"additional","affiliation":[{"name":"Moscow Clinical Research Center \u201cHospital No. 52\u201d, 3, Pekhotnaya St., Moscow 123182, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8414-1545","authenticated-orcid":false,"given":"Yuliya A.","family":"Gavrikova","sequence":"additional","affiliation":[{"name":"Moscow Clinical Research Center \u201cHospital No. 52\u201d, 3, Pekhotnaya St., Moscow 123182, Russia"},{"name":"Research Institute of Healthcare Organization and Medical Management, Moscow Department of Healthcare, 30, Bolshaya Tatarskaya St., Moscow 115184, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8007-5499","authenticated-orcid":false,"given":"Vladislav V.","family":"Dolgov","sequence":"additional","affiliation":[{"name":"Moscow Clinical Research Center \u201cHospital No. 52\u201d, 3, Pekhotnaya St., Moscow 123182, Russia"},{"name":"Research Institute of Healthcare Organization and Medical Management, Moscow Department of Healthcare, 30, Bolshaya Tatarskaya St., Moscow 115184, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7894-9222","authenticated-orcid":false,"given":"Anastasiia A.","family":"Buianova","sequence":"additional","affiliation":[{"name":"Moscow Clinical Research Center \u201cHospital No. 52\u201d, 3, Pekhotnaya St., Moscow 123182, Russia"},{"name":"Russian Clinical Research Center of Gerontology, Pirogov Russian National Research Medical University of the Ministry of Healthcare of the Russian Federation, Moscow 129226, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina D.","family":"Glumova","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1894-9458","authenticated-orcid":false,"given":"Maria I.","family":"Tubalova","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5664-492X","authenticated-orcid":false,"given":"Galina S.","family":"Koksharova","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0553-1316","authenticated-orcid":false,"given":"Artem R.","family":"Nurislamov","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim I.","family":"Mazurov","sequence":"additional","affiliation":[{"name":"Organizational and Methodological Department, North-Western State Medical University Named After I.I. Mechnikov, 41, Kirochnaya St., Saint Petersburg 191015, Russia"},{"name":"Clinical Rheumatology Hospital No. 25 Named After V.A. Nasonova, 30, Bolshaya Podyacheskaya St., Saint Petersburg 190068, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e509","DOI":"10.1002\/mco2.509","article-title":"Rheumatoid Arthritis: Pathogenesis and Therapeutic Advances","volume":"5","author":"Gao","year":"2024","journal-title":"MedComm"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1038\/s41588-022-01213-w","article-title":"Multi-Ancestry Genome-Wide Association Analyses Identify Novel Genetic Mechanisms in Rheumatoid Arthritis","volume":"54","author":"Ishigaki","year":"2022","journal-title":"Nat. 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