{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:10:30Z","timestamp":1753877430691,"version":"3.41.2"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,6]]},"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n TNF-\u03b1 is a pro-inflammatory cytokine that has been implicated in many inflammatory diseases, but its association with idiopathic nephrotic syndrome (INS) is poorly understood. This study looked for an association of TNF-\u03b1 gene polymorphisms with INS, as well as its effect on steroid responsiveness among Kuwaiti Arab children.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Genotypes of the TNF-a gene polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism in 151 INS Kuwaiti Arab patients and 64 age and sex-matched controls. Clinical data of all subjects were reviewed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The heterozygous AG genotype was detected in 8.6% of INS patients compared 23.4% of the controls (p\u2009&lt;\u20090.01). Comparing steroid responsiveness, AA genotype was significantly more common in steroid-sensitive nephrotic syndrome (SSNS) cases than steroid-resistant nephrotic syndrome (SRNS) patients (p\u2009=\u20090.001). However, AG genotype was significantly more common in SRNS patients compared to the SSNS cases (p\u2009=\u20090.001). No difference was found between these two subgroups in the GG genotype frequency.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n AG genotype of TNF-a gene polymorphisms may be considered a suitable marker for INS disease among Kuwaiti children. Both AA and AG genotypes may be useful in predicting steroid responsiveness among these cases of Arab ethnicity. The findings might open the era for the use of genetic markers in the early treatment of NS.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/tropej\/fmad047","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T03:32:14Z","timestamp":1702956734000},"source":"Crossref","is-referenced-by-count":0,"title":["Tumor necrosis factor alpha gene polymorphism affects the pattern of idiopathic nephrotic syndrome in Kuwaiti Arab children"],"prefix":"10.1093","volume":"70","author":[{"suffix":"MD","given":"Amal A","family":"Al-Eisa","sequence":"first","affiliation":[{"name":"Department of Pediatrics, College of Medicine\u2014Kuwait University , Kuwait City, Safat 13110, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6148-1707","authenticated-orcid":false,"given":"Maysoun","family":"Al Rushood","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine\u2014Kuwait University , Kuwait City, Safat 13110, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumedha","family":"Kashyap","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine\u2014Kuwait University , Kuwait City, Safat 13110, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Z","family":"Haider","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine\u2014Kuwait University , Kuwait City, Safat 13110, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"2023121903314949100_fmad047-B1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00467-008-1051-3","article-title":"Familial forms of nephrotic syndrome","volume":"25","author":"Caridi","year":"2010","journal-title":"Pediatr Nephrol"},{"key":"2023121903314949100_fmad047-B2","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/s10157-015-1216-x","article-title":"Evidence-based clinical practice guidelines for nephrotic syndrome 2014","volume":"20","author":"Nishi","year":"2016","journal-title":"Clin Exp Nephrol"},{"key":"2023121903314949100_fmad047-B3","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1080\/15513815.2016.1225872","article-title":"Glomerular glucocorticoid receptors expression and clinicopathological types of childhood nephrotic syndrome","volume":"36","author":"Gamal","year":"2017","journal-title":"Fetal Pediatr Pathol"},{"key":"2023121903314949100_fmad047-B4","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1007\/s004679900269","article-title":"Circulating mediators of proteinuria in idiopathic minimal lesion nephrotic syndrome","volume":"14","author":"Garin","year":"2000","journal-title":"Pediatr Nephrol"},{"key":"2023121903314949100_fmad047-B5","doi-asserted-by":"crossref","first-page":"a030338","DOI":"10.1101\/cshperspect.a030338","article-title":"T helper cell differentiation, heterogeneity, and plasticity","volume":"10","author":"Zhu","year":"2018","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2023121903314949100_fmad047-B6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.3389\/fimmu.2020.00289","article-title":"Editorial: T cell differentiation and function in tissue inflammation","volume":"11","author":"Goswami","year":"2020","journal-title":"Front Immunol"},{"key":"2023121903314949100_fmad047-B7","first-page":"5","article-title":"Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. 1986","volume":"175","author":"Mosmann","year":"2005","journal-title":"J Immunol"},{"key":"2023121903314949100_fmad047-B8","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1038\/s41423-019-0220-6","article-title":"Helper T cell differentiation","volume":"16","author":"Saravia","year":"2019","journal-title":"Cell Mol Immunol"},{"key":"2023121903314949100_fmad047-B9","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1136\/ard.61.3.213","article-title":"Differential association of polymorphisms in the TNF-alpha region with psoriatic arthritis but not psoriasis","volume":"61","author":"Hohler","year":"2002","journal-title":"Ann. Rheum. Dis"},{"key":"2023121903314949100_fmad047-B10","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.bbadis.2009.01.007","article-title":"Tumor necrosis factor alpha \u2212308 gene locus promoter polymorphism: an analysis of association with health and disease","volume":"1792","author":"Elahi","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"2023121903314949100_fmad047-B11","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jbspin.2014.08.006","article-title":"Analysis of association between polymorphisms within genes coding for tumor necrosis factor (TNF)-alpha and TNF receptors and responsiveness to TNF-alpha blockers in patients with rheumatoid arthritis","volume":"82","author":"Swierkot","year":"2015","journal-title":"Joint Bone Spine"},{"key":"2023121903314949100_fmad047-B12","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1136\/ard.2007.080440","article-title":"The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumor necrosis factor alpha expression in the synovium","volume":"67","author":"Wijbrandts","year":"2008","journal-title":"Ann Rheum Dis"},{"key":"2023121903314949100_fmad047-B13","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/ar1465","article-title":"Circulating tumor necrosis factor-alpha bioactivity in rheumatoid arthritis patients treated with infliximab: link to clinical response","volume":"7","author":"Marotte","year":"2005","journal-title":"Arthritis Res. Ther"},{"key":"2023121903314949100_fmad047-B14","doi-asserted-by":"crossref","first-page":"e104354","DOI":"10.1371\/journal.pone.0104354","article-title":"Circulating TNF receptors are significant prognostic biomarkers for idiopathic membranous nephropathy","volume":"9","author":"Lee","year":"2014","journal-title":"PLoS One"},{"key":"2023121903314949100_fmad047-B15","first-page":"84","article-title":"Association of cytokine genes polymorphisms and the response to corticosteroid therapy in children with idiopathic nephrotic syndrome: a pilot study in Egypt","volume":"2","author":"Madani","year":"2014","journal-title":"Int Res J Med Med Sci"},{"key":"2023121903314949100_fmad047-B16","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.cyto.2017.06.021","article-title":"Tumor necrosis factor alpha gene polymorphisms and haplotypes in Egyptian children with nephrotic syndrome","volume":"102","author":"Youssef","year":"2018","journal-title":"Cytokine"},{"key":"2023121903314949100_fmad047-B17","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook","year":"1989","edition":"2nd ed"},{"key":"2023121903314949100_fmad047-B18","doi-asserted-by":"crossref","first-page":"383","DOI":"10.4103\/0019-5359.44017","article-title":"Does cytokine gene polymorphism affect steroid responses in idiopathic nephrotic syndrome?","volume":"62","author":"Agrawal","year":"2008","journal-title":"Indian J Med Sci"},{"key":"2023121903314949100_fmad047-B19","doi-asserted-by":"crossref","first-page":"698","DOI":"10.3892\/br.2017.908","article-title":"Evaluation of tumor necrosis factor (TNF)-\u03b1 mRNA expression level and the rs1799964 polymorphism of the TNF-\u03b1 gene in peripheral mononuclear cells of patients with inflammatory bowel diseases","volume":"6","author":"Nourian","year":"2017","journal-title":"Biomed Rep"},{"key":"2023121903314949100_fmad047-B20","doi-asserted-by":"crossref","first-page":"2662","DOI":"10.1111\/jocd.14940","article-title":"TNF-\u03b1 gene -238G>A polymorphism is associated with psoriasis patients","volume":"21","author":"Akc\u0131lar","year":"2022","journal-title":"J Cosmet Dermatol"},{"key":"2023121903314949100_fmad047-B21","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1007\/s00296-021-05016-w","article-title":"Association of polymorphisms in promoter region of TNF-\u03b1 -238 and -308 with clinical outcomes in patients with immune-mediated inflammatory diseases on anti-TNF therapy","volume":"41","author":"Miler","year":"2021","journal-title":"Rheumatol Int"},{"key":"2023121903314949100_fmad047-B22","doi-asserted-by":"crossref","first-page":"955812","DOI":"10.3389\/fimmu.2022.955812","article-title":"TNF-\u03b1 inhibitor ameliorates immune-related arthritis and pneumonitis in humanized mice","volume":"13","author":"Gao","year":"2022","journal-title":"Front Immunol"},{"key":"2023121903314949100_fmad047-B23","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1007\/s00467-012-2163-3","article-title":"TNF\u03b1 pathway blockade ameliorates toxic effects of FSGS plasma on podocyte cytoskeleton and \u03b23 integrin activation","volume":"27","author":"Bitzan","year":"2012","journal-title":"Pediatr Nephrol"},{"key":"2023121903314949100_fmad047-B24","doi-asserted-by":"crossref","first-page":"9086","DOI":"10.3390\/ijms23169086","article-title":"Tumor necrosis factor-\u03b1-induced C-C motif chemokine ligand 20 expression through TNF receptor 1-dependent activation of EGFR\/p38 MAPK and JNK1\/2\/FoxO1 or the NF-\u03baB pathway in human cardiac fibroblasts","volume":"23","author":"Yang","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2023121903314949100_fmad047-B25","first-page":"1169","article-title":"Recovery of ischemic limb and femoral artery endothelial function are preserved in mice with dextran sodium sulfate-induced chronic colitis","volume":"11","author":"Wu","year":"2022","journal-title":"Biology (Basel)"},{"key":"2023121903314949100_fmad047-B26","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3892\/etm.2020.9215","article-title":"Correlation of TNF-\u03b1 and IL-10 gene polymorphisms with primary nephrotic syndrome","volume":"20","author":"Xiao","year":"2020","journal-title":"Exp Ther Med"},{"key":"2023121903314949100_fmad047-B27","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1007\/s12291-011-0126-2","article-title":"Cytokine gene polymorphism in idiopathic nephrotic syndrome children","volume":"26","author":"Jafar","year":"2011","journal-title":"Indian J Clin Biochem"},{"key":"2023121903314949100_fmad047-B28","first-page":"164","article-title":"Preliminary study regarding the association between tumor necrosis factor alpha gene polymorphisms and childhood idiopathic nephrotic syndrome in romanian pediatric patients","volume":"12","author":"Tieranu","year":"2017","journal-title":"Maedica (Bucur)"},{"key":"2023121903314949100_fmad047-B29","first-page":"95","article-title":"Lack of association between TNF-alpha rs 1800629 (\u2212308G > A) polymorphism and nephrotic syndrome","volume":"1","author":"Sadeghi-Bojd","year":"2021","journal-title":"Iran J. Kidney Dis"},{"key":"2023121903314949100_fmad047-B30","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/rheumatology\/kel175","article-title":"The \u2212308 tumor necrosis factor-alpha gene polymorphism predicts therapeutic response to TNF (alpha)-blockers in rheumatoid arthritis and spondyloarthritis patients","volume":"46","author":"Seitz","year":"2007","journal-title":"Rheumatology (Oxford)"},{"key":"2023121903314949100_fmad047-B31","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1007\/s00467-015-3057-y","article-title":"Viral-associated glomerulopathies in children","volume":"30","author":"Wenderfer","year":"2015","journal-title":"Pediatr Nephrol"},{"key":"2023121903314949100_fmad047-B32","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1080\/20469047.2017.1374002","article-title":"Childhood nephrotic syndrome in tropical Africa: then and now","volume":"37","author":"Olowu","year":"2017","journal-title":"Paediatr Int Child Health"}],"container-title":["Journal of Tropical Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/tropej\/article-pdf\/70\/1\/fmad047\/54587152\/fmad047.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/tropej\/article-pdf\/70\/1\/fmad047\/54587152\/fmad047.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T03:32:31Z","timestamp":1702956751000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/tropej\/article\/doi\/10.1093\/tropej\/fmad047\/7477883"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,6]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,12,6]]}},"URL":"https:\/\/doi.org\/10.1093\/tropej\/fmad047","relation":{},"ISSN":["1465-3664"],"issn-type":[{"type":"electronic","value":"1465-3664"}],"subject":[],"published-other":{"date-parts":[[2024,2,1]]},"published":{"date-parts":[[2023,12,6]]},"article-number":"fmad047"}}