title: Polymorphism in tumor necrosis factor genes associated with mucocutaneous leishmaniasis.
abstract: 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 < 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 < 0.001) compared with males (RR = 4; P < 0.05). A significantly higher frequency (P < 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 < 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.
authors.affiliation: Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Cabrera
authors.forename: M A
authors.initials: MA
authors.lastname: Shaw
authors.forename: C
authors.initials: C
authors.lastname: Sharples
authors.forename: H
authors.initials: H
authors.lastname: Williams
authors.forename: M
authors.initials: M
authors.lastname: Castes
authors.forename: J
authors.initials: J
authors.lastname: Convit
authors.forename: J M
authors.initials: JM
authors.lastname: Blackwell
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D007897:Leishmaniasis, Mucocutaneous / Q000235:genetics* / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*; D014687:Venezuela / Q000453:epidemiology
chemical_list: D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha