title: TNF promoter -308 G>A and LTA 252 A>G polymorphisms in Portuguese patients with systemic lupus erythematosus.
abstract: The polymorphism of the tumor necrosis factor (TNF) promoter gene at position -308 and that of the lymphotoxin alpha (LTA) gene at position 252 have been implicated as genetic risk factors for systemic lupus erythematosus (SLE) in some populations. In a nested case-control study, we investigated the possible association of these polymorphisms with susceptibility to SLE and with phenotypic disease features in Portuguese Caucasian patients. TNF-308 G>A and LTA 252 A>G polymorphisms were determined by restriction fragment length polymorphism analysis in a cohort of 115 SLE patients and 152 unrelated healthy controls, and the magnitude of the association between genotypes and SLE diagnosis was calculated. For SLE patients, we also tested the association between disease characteristics and genotypes. No significant differences in genotype or allele frequencies could be identified between SLE cases and controls. Lupus nephritis (OR = 2.84; 95%CI 1.14-7.03, P = 0.02) and the presence of anti-Sm antibodies (OR = 3.11; 95%CI 1.08-8.94; P = 0.03) were significantly more prevalent among lupus patients possessing the TNF-308 A allele. The occurrence of nephritis was also higher in LTA 252 G allele carriers (OR = 2.90; 95%CI 1.12-7.54; P = 0.02). Our results do not support a major role of either the TNF-308 G>A or the LTA 252 A>G polymorphisms as genetic risk factors for SLE. Nevertheless, these polymorphisms appear to associate with the risk of renal lupus and distinct immunological features.
authors.affiliation: Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. mjps@netvisao.pt
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Santos
authors.forename: Diana
authors.initials: D
authors.lastname: Carmona-Fernandes
authors.forename: Joana
authors.initials: J
authors.lastname: Caetano-Lopes
authors.forename: Inês P
authors.initials: IP
authors.lastname: Perpétuo
authors.forename: Bruno
authors.initials: B
authors.lastname: Vidal
authors.forename: Susana
authors.initials: S
authors.lastname: Capela
authors.forename: José
authors.initials: J
authors.lastname: Canas da Silva
authors.forename: João Eurico
authors.initials: JE
authors.lastname: Fonseca
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011174:Portugal / Q000453:epidemiology; D015995:Prevalence; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D001323:Autoantibodies; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha