Contribution for new genetic markers of rheumatoid arthritis activity and severity: Sequencing of the tumor necrosis factor-alpha gene promoter

João Eurico Fonseca, João Cavaleiro, José Teles, Elsa Sousa, Valeska L. Andreozzi, Marília Antunes, Maria Antonia Amaral-Turkman, Helena Canhão, Ana Filipa Mourão, Joana Caetano-Lopes, Pamela Weinmann, Marta Sobral, Patrícia Nero, Maria J. Saavedra, Armando Malcata, Margarida Cruz, Rui Melo, Araceli Braña, Luis Miranda, José V. PattoAnabela Barcelos, José Canas da Silva, Luís M. Santos, Guilherme Figueiredo, Mário Rodrigues, Herberto Jesus, Alberto Quintal, Teresa Carvalho, José A.Pereira da Silva, Jaime Branco, Mário Viana Queiroz

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Abstract

The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-α) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-α gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-α promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.

Original languageEnglish
Article numberR37
Pages (from-to)Online
JournalArthritis Research and Therapy
Volume9
DOIs
Publication statusPublished - 4 Apr 2007

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