{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:27:30Z","timestamp":1791041250723,"version":"4.1.0"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1995,11,1]]},"abstract":"<jats:p>Recent studies have shown that mucocutaneous leishmaniasis (MCL), a severe and debilitating form of American cutaneous leishmaniasis (ACL) caused by Leishmania braziliensis infection, is accompanied by high circulating levels of tumor necrosis factor (TNF)-alpha. Analysis of TNF polymorphisms in Venezuelan ACL patients and endemic unaffected controls demonstrates a high relative risk (RR) of 7.5 (P &amp;lt; 0.001) of MCL disease in homozygotes for allele 2 of a polymorphism in intron 2 of the TNF-beta gene, especially in females (RR = 9.5; P &amp;lt; 0.001) compared with males (RR = 4; P &amp;lt; 0.05). A significantly higher frequency (P &amp;lt; 0.05) of allele 2 at the -308-basepair TNF-alpha gene polymorphism was also observed in MCL patients (0.18) compared with endemic control subjects (0.069), again associated with a high relative risk of disease (RR = 3.5; P &amp;lt; 0.05) even in the heterozygous condition. Because both the TNF-alpha and TNF-beta polymorphisms have previously been linked with functional differences in TNF-alpha levels, these data suggest that susceptibility to the mucocutaneous form of disease may be directly associated with regulatory polymorphisms affecting TNF-alpha production.<\/jats:p>","DOI":"10.1084\/jem.182.5.1259","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"1259-1264","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":357,"title":["Polymorphism in tumor necrosis factor genes associated with mucocutaneous leishmaniasis."],"prefix":"10.1084","volume":"182","author":[{"given":"M","family":"Cabrera","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Sharples","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Castes","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Convit","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J M","family":"Blackwell","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1995,11,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/182\/5\/1259\/1677974\/1259.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/182\/5\/1259\/1677974\/1259.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T07:03:08Z","timestamp":1690268588000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/182\/5\/1259\/25763\/Polymorphism-in-tumor-necrosis-factor-genes"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,11,1]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1995,11,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.182.5.1259","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,11,1]]}}}