{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T13:13:22Z","timestamp":1778764402065,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/f1000research.172631.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000}}],"reference-count":31,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    Background Ankylosing spondylitis (AS) is a chronic inflammatory illness mainly influencing the axial skeleton. It is a multifactorial illness in which environmental and genetic parameters contribute to its cause, one of which is interleukins, including interleukin-18 (IL-18). Therefore, this study aimed to investigate the association between single nucleotide polymorphism (SNP) rs549908 and serum levels of IL-18 in Iraqi patients with AS. Methods During the period of November 2024 and January 2025, a total of 100 individuals were enrolled in the present work, including 50 patients with AS and 50 healthy controls (HC), were obtained from Baghdad Teaching Hospital. Using enzyme-linked immunosorbent assay (ELISA) and TaqMan real-time polymerase chain reaction (PCR), serum levels and rs549908 genotyping of IL-18 were estimated. Results Significantly, levels of IL-18 in serum were raised in patients with AS compared to HC (235.7060\n                    <ns3:italic>vs.<\/ns3:italic>\n                    151.10 pg\/mL, p &lt; 0.001). Genetically, T allele frequency (69.0% vs. 49.0%,\n                    <ns3:italic>p =<\/ns3:italic>\n                    0.006) and TT genotype frequency (53.1% vs. 23.5%,\n                    <ns3:italic>p =<\/ns3:italic>\n                    0.004) were significantly greater in patients with AS compared to HC. Analysis under the model of dominant (TG + GG\n                    <ns3:italic>vs.<\/ns3:italic>\n                    TT) demonstrated significant association between status of illness and genotype (OR = 0.29,\n                    <ns3:italic>p =<\/ns3:italic>\n                    0.007). Conclusions These outcomes suggest rs549908 SNP and serum levels of IL-18, are related with increased susceptibility to AS in the Iraqi population.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.172631.2","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T12:54:15Z","timestamp":1778763255000},"page":"1399","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Promoter Variants in Interleukin-18 on Susceptibility to Ankylosing Spondylitis in a Sample of Iraqi Patients"],"prefix":"10.12688","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7264-4899","authenticated-orcid":false,"given":"Ibtehal Kadhim","family":"Jasim","sequence":"first","affiliation":[{"name":"Biotechnology Baghdad Baghdad Governorate University of Baghdad"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asmaa Mohammed","family":"Saud","sequence":"additional","affiliation":[{"name":"Biotechnology Baghdad Baghdad Governorate University of Baghdad"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"155002","DOI":"10.1016\/j.cyto.2020.155002","article-title":"Immunological and oxidative stress biomarkers in ankylosing spondylitis patients with or without metabolic syndrome.","volume":"128","author":"A Pishgahi","year":"2020","journal-title":"Cytokine."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"94-102","DOI":"10.1111\/imm.13242","article-title":"New developments in our understanding of ankylosing spondylitis pathogenesis.","volume":"161","author":"A Voruganti","year":"2020","journal-title":"Immunology."},{"key":"ref3","first-page":"426-431","article-title":"Evaluation of Apelin and Tartrate-Resistant Acid Phosphatase-5b in Ankylosing Spondylitis Male Patients With and Without Osteoporosis.","volume":"60","author":"I Salem","year":"2019","journal-title":"Iraqi J. Sci."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.3390\/biom10101461","article-title":"Understanding the pathogenesis of spondyloarthritis.","volume":"10","author":"A Sharip","year":"2020","journal-title":"Biomolecules."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"6008","DOI":"10.3390\/ijms20236008","article-title":"Cytokines in inflammatory disease.","volume":"20","author":"S Kany","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"291-297","DOI":"10.2147\/IJGM.S509296","article-title":"Anti-osteoporosis is imperative in prevention of progress of ankylosing spondylitis.","volume":"18","author":"B Zheng","year":"2025","journal-title":"Int. J. Gen. Med."},{"key":"ref7","first-page":"823-831","article-title":"Interleukin-18, interleukin-20, and matrix metalloproteinases (MMP-1, MMP-3) as markers of psoriatic arthritis disease severity and their correlations with biomarkers of inflammation and turnover of joint cartilage.","volume":"37","author":"M Waszczykowski","year":"2020","journal-title":"Postepy Dermatol. Alergol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"257-264","DOI":"10.3855\/jidc.9813","article-title":"Interleukin-18 and its gene single nucleotide polymorphisms (SNPs) influence chronic hepatitis C progression.","volume":"12","author":"E Said","year":"2018","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"107089","DOI":"10.1016\/j.phrs.2024.107089","article-title":"Interleukin-18 in chronic pain: Focus on pathogenic mechanisms and potential therapeutic targets.","volume":"201","author":"J Ju","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1186\/s12920-023-01744-z","article-title":"Evaluation of causal associations between interleukin-18 levels and immune-mediated inflammatory diseases: a Mendelian randomization study.","volume":"16","author":"J Wu","year":"2023","journal-title":"BMC Med. Genet."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"951535","DOI":"10.3389\/fimmu.2022.951535","article-title":"Pathogenic roles and diagnostic utility of interleukin-18 in autoinflammatory diseases.","volume":"13","author":"M Shimizu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"178-183","DOI":"10.1016\/j.diabres.2016.09.021","article-title":"Interleukin-18 gene polymorphism and risk of cardiovascular disease in older patients with type 2 diabetes mellitus.","volume":"121","author":"M Buraczynska","year":"2016","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref13","first-page":"2367","article-title":"IL-18 gene rs187238 and rs1946518 polymorphisms and expression in gingival tissue in individuals with periodontitis.","volume":"10","author":"M Mazurek-Mochol","year":"2022","journal-title":"Biomedicine."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"269-274","DOI":"10.1016\/j.gene.2017.05.034","article-title":"Genetic variants of interleukin-18 are associated with reduced risk of atrial fibrillation in a population from Northeast China.","volume":"626","author":"W Wang","year":"2017","journal-title":"Gene."},{"key":"ref15","first-page":"203-209","article-title":"Associations between interleukin-18 gene polymorphisms and susceptibility to vasculitis: A meta-analysis.","volume":"37","author":"J Jung","year":"2020","journal-title":"Sarcoidosis Vasc. Diffuse Lung Dis."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"777-783","DOI":"10.1136\/ard.2009.108233","article-title":"The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection.","volume":"68","author":"M Rudwaleit","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref17","first-page":"78-83","article-title":"Ankylosing spondylitis functional and activity indices in clinical practice.","volume":"7","author":"C Popescu","year":"2014","journal-title":"J. Med. Life."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"257-266","DOI":"10.1007\/s12079-019-00544-4","article-title":"A comprehensive pathway map of IL-18-mediated signalling.","volume":"14","author":"D Rex","year":"2020","journal-title":"J. Cell Commun. 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Sci."},{"key":"ref22","doi-asserted-by":"crossref","first-page":"54-62","DOI":"10.1111\/iji.70027","article-title":"The Impact of TLR4 rs41426344 Polymorphism on Ankylosing Spondylitis Disease Activity: A Study in Turkish Patients.","volume":"53","author":"D Kirkik","year":"2026","journal-title":"Int. J. Immunogenet."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"328-337","DOI":"10.21608\/jbaar.2024.292204.1048","article-title":"Strong Association of STIP1 Gene rs2236647 Polymorphism and Serum Magnesium Level with Bronchial Asthma in a Population from Iraq.","author":"A Saud","year":"2024","journal-title":"J. Biosci. Appl. Res."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1-35","DOI":"10.21931\/RB\/2023.08.02.28","article-title":"Relationship between Toll-like Receptors and pathogenesis of Systemic Lupus Erythematosus.","volume":"8","author":"B Ratib","year":"2023","journal-title":"Revis Bionatura."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1186\/s40001-024-01846-z","article-title":"Assessment of interleukin-18 gene polymorphism and serum levels in cutaneous lichen planus.","volume":"29","author":"R Doss","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"228-231","DOI":"10.1016\/j.gene.2018.07.071","article-title":"Association of IL18 genetic polymorphisms with increased risk of biliary atresia susceptibility in Southern Chinese children.","volume":"677","author":"J Liang","year":"2018","journal-title":"Gene."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"3963","DOI":"10.3390\/jcm12123963","article-title":"IL18 gene polymorphism is associated with total IgE in adult subjects with asthma.","volume":"12","author":"V Lando","year":"2023","journal-title":"J. Clin. Med."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"34-44","DOI":"10.21608\/fumj.2025.326668.1404","article-title":"Interleukins gene polymorphism in alopecia areata patients: a systematic review.","volume":"15","author":"N Aboraia","year":"2025","journal-title":"Fayoum Univ. Med. 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The manuscript has been thoroughly revised to improve language clarity and style. Expressions such as \u201crelations among\u201d and \u201cillness activity\u201d have been corrected, and repetitive and complex sentences have been simplified. The statistical analysis section has been revised for clarity and consistency. The use of inappropriate terms such as \u201cextremely significant\u201d has been removed, and Hardy\u2013Weinberg equilibrium calculations have been rechecked. The ROC analysis has been clarified to better reflect its diagnostic relevance. As suggested, the discussion has been strengthened by incorporating recent evidence on immune-related genetic variants, including the study by Kirkik et al. (2026). We believe these revisions have substantially improved the manuscript and addressed all concerns raised. Sincerely, The Authors","URL":"https:\/\/f1000research.com\/articles\/14-1399\/v2#referee-comment-16116","order":1,"name":"referee-comment-16116","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.190371.r475866, Raghad Hassan Hussein, Department of Medical laboratory Techniques, College of health and medical techniques, Middle Technical University, Baghdad, 25 Apr 2026, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/14-1399\/v1#referee-response-475866","order":2,"name":"referee-response-475866","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Ibtehal kadhim<\/b>; \n<i>Posted: 01 May 2026<\/i>; Dear Reviewer, We thank you for your positive evaluation and helpful comments. The manuscript has been revised to improve clarity and readability. Terminology has been standardized throughout the text, including replacing \u201crelations among\u201d with \u201cassociation between\u201d and \u201cillness activity\u201d with \u201cdisease activity\u201d. These revisions have improved the overall quality of the manuscript. Sincerely, The Authors","URL":"https:\/\/f1000research.com\/articles\/14-1399\/v2#referee-comment-16117","order":3,"name":"referee-comment-16117","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.190371.r475867, Sahar m Hussein, Al-Nahrain University, Baghdad, 30 Apr 2026, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/14-1399\/v1#referee-response-475867","order":4,"name":"referee-response-475867","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Ibtehal kadhim<\/b>; \n<i>Posted: 01 May 2026<\/i>; Dear Reviewer, We sincerely thank you for your constructive and encouraging comments. The manuscript has been revised to improve language clarity and reduce repetition. Statistical reporting has been refined for better consistency. The ROC analysis has been clarified, and the discussion has been strengthened by incorporating additional relevant studies. We believe these revisions have improved the manuscript. Sincerely, The Authors","URL":"https:\/\/f1000research.com\/articles\/14-1399\/v2#referee-comment-16118","order":5,"name":"referee-comment-16118","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":6,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}