{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T23:02:50Z","timestamp":1780441370163,"version":"3.54.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis is a life-threatening condition caused by dysregulated immune responses, leading to inflammation, tissue damage, and organ failure. This study investigates the role of the IL-18 rs187238 (\u2212137C&amp;gt;G) polymorphism in sepsis susceptibility, progression, and patient prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A multicenter case-control study was conducted with 784 sepsis patients and 776 healthy controls. The IL-18 rs187238 polymorphism was genotyped using imLDR\u2122 multiplex SNP genotyping method. ELISA and qRT-PCR were used to detect related inflammatory cytokine expression, while functional analysis was performed using dual-luciferase assays to evaluate the impact of the rs187238 variant on IL-18 promoter activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We observed a significant association between the rs187238 polymorphism and 28-day ICU mortality in sepsis patients. The CG\/GG genotypes (OR = 1.470, 95% CI = 1.029\u20132.129,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.037) were more frequently observed in non-survivors compared to survivors, with a notable difference in the frequency of the G allele (OR = 1.534, 95% CI = 1.111\u20132.133,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.010). Kaplan-Meier survival analysis confirmed that patients with CG\/GG genotypes had significantly lower 28-day survival rates compared to those with the CC genotype (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.028). However, no significant differences in genotype and allele frequencies were observed between cases and healthy controls, nor between sepsis and septic shock patients. Sepsis patients with CG\/GG genotypes had significantly higher IL-18 levels than those with the CC genotype. Dual-luciferase assays confirmed that the G allele increased IL-18 promoter activity, supporting its genetic influence on IL-18 expression. Additionally, sepsis patients with CG\/GG genotypes expressed significantly increased levels of IL-1\u03b2, IL-6, and ICAM-1 than those with CC genotype. IL-18 treatment enhanced the expression of IL-1\u03b2, IL-6, IL-27, TNF-\u03b1, and MCP-1 in THP-1 macrophages upon LPS stimulation. In HUVECs, IL-18 treatment further enhanced LPS-induced IL-6, IL-27, TNF-\u03b1, and ICAM-1 expression, while promoting apoptosis and reducing VE-cadherin levels, emphasizing its role in inflammation and endothelial dysfunction in sepsis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The IL-18 rs187238\u00a0C&amp;gt;G polymorphism is linked to higher IL-18 expression and intensified inflammatory responses, which are associated with poor sepsis prognosis. The sepsis-associated risk rs187238-G allele serves as a potential prognostic biomarker for sepsis-related mortality. Targeting IL-18 or its genetic variations might offer new avenues for sepsis therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1820930","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T22:10:22Z","timestamp":1780438222000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic variation at the IL-18\u2013137C&gt;G is associated with poor sepsis prognosis and enhanced inflammatory responses: a multicenter hospital-based study"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhuoji","family":"Li","sequence":"first","affiliation":[{"name":"Jinan University","place":["Guangzhou, Guangdong, China"]},{"name":"The Intensive Care Unit, The Second Affiliated Hospital, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanjie","family":"Gu","sequence":"additional","affiliation":[{"name":"Jinan University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhen","family":"Liu","sequence":"additional","affiliation":[{"name":"The Intensive Care Unit, The First Dongguan Affiliated Hospital, Guangdong Medical University","place":["Dongguan, Guangdong, China"]},{"name":"The Intensive Care Unit, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiekai","family":"Li","sequence":"additional","affiliation":[{"name":"The Intensive Care Unit, Jieyang People\u2019s Hospital","place":["Jieyang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manting","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Intensive Care Unit, Jieyang People\u2019s Hospital","place":["Jieyang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanchun","family":"Yang","sequence":"additional","affiliation":[{"name":"The Intensive Care Unit, Jieyang People\u2019s Hospital","place":["Jieyang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiting","family":"Yang","sequence":"additional","affiliation":[{"name":"The Intensive Care Unit, The First Dongguan Affiliated Hospital, Guangdong Medical University","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Intensive Care Unit, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]},{"name":"The Intensive Care Unit, Jieyang People\u2019s Hospital","place":["Jieyang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Zhong","sequence":"additional","affiliation":[{"name":"The Intensive Care Unit, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]},{"name":"The Intensive Care Unit, Jieyang People\u2019s Hospital","place":["Jieyang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchun","family":"Liu","sequence":"additional","affiliation":[{"name":"The Intensive Care Unit, Jieyang People\u2019s Hospital","place":["Jieyang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbing","family":"He","sequence":"additional","affiliation":[{"name":"The Intensive Care Unit, Jieyang People\u2019s Hospital","place":["Jieyang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Yin","sequence":"additional","affiliation":[{"name":"Jinan University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Shao","sequence":"additional","affiliation":[{"name":"Jinan University","place":["Guangzhou, Guangdong, China"]},{"name":"The Intensive Care Unit, The First Dongguan Affiliated Hospital, Guangdong Medical University","place":["Dongguan, Guangdong, China"]},{"name":"The Intensive Care Unit, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4923","DOI":"10.1128\/IAI.05601-11","article-title":"Functional promoter haplotypes of interleukin-18 condition susceptibility to severe malarial anemia and childhood mortality","volume":"79","author":"Anyona","year":"2011","journal-title":"Infect. 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