TNF promoter -308 G>A and LTA 252 A>G polymorphisms in Portuguese patients with systemic lupus erythematosus

• Published in: Rheumatology international 2012-08, Vol.32 (8), p.2239-2244
• Main Authors: Santos, Maria José, Carmona-Fernandes, Diana, Caetano-Lopes, Joana, Perpétuo, Inês P., Vidal, Bruno, Capela, Susana, Canas da Silva, José, Fonseca, João Eurico
• Format: Article
• Language: English
• Subjects: Adult; Autoantibodies - blood; Case-Control Studies; Chi-Square Distribution; European Continental Ancestry Group - genetics; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - ethnology; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Nephritis - genetics; Lupus Nephritis - immunology; Lymphotoxin-alpha - genetics; Male; Medicine; Medicine & Public Health; Middle Aged; Odds Ratio; Original Article; Phenotype; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Portugal - epidemiology; Prevalence; Promoter Regions, Genetic; Rheumatology; Risk Assessment; Risk Factors; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0172-8172; 1437-160X
• DOI: 10.1007/s00296-011-1950-7

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.