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

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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.

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Acknowledgments

This work was supported by a grant from Fundação para a Ciência e a Tecnologia, Portugal (PIC/IC/82920/2007) and by an unrestricted grant from Wyeth Portugal.

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Authors and Affiliations

  1. Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal

    Maria José Santos, Diana Carmona-Fernandes, Joana Caetano-Lopes, Inês P. Perpétuo, Bruno Vidal & João Eurico Fonseca

  2. Rheumatology, Hospital Garcia de Orta, Almada, Portugal

    Maria José Santos & José Canas da Silva

  3. Rheumatology and Bone Metabolic Diseases, Hospital Santa Maria, Lisbon, Portugal

    Susana Capela & João Eurico Fonseca

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  1. Maria José Santos
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  2. Diana Carmona-Fernandes
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  3. Joana Caetano-Lopes
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  4. Inês P. Perpétuo
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  8. João Eurico Fonseca
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Correspondence to Maria José Santos.

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Santos, M.J., Carmona-Fernandes, D., Caetano-Lopes, J. et al. TNF promoter -308 G>A and LTA 252 A>G polymorphisms in Portuguese patients with systemic lupus erythematosus. Rheumatol Int 32, 2239–2244 (2012). https://doi.org/10.1007/s00296-011-1950-7

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  • DOI: https://doi.org/10.1007/s00296-011-1950-7

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