title: Contribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoter.
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-alpha) 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-alpha 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-alpha 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.
authors.affiliation: Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av, Professor Egas Moniz, 1649-028, Lisboa, Portugal. jefonseca@netcabo.pt
authors.forename: João Eurico
authors.initials: JE
authors.lastname: Fonseca
authors.forename: João
authors.initials: J
authors.lastname: Cavaleiro
authors.forename: José
authors.initials: J
authors.lastname: Teles
authors.forename: Elsa
authors.initials: E
authors.lastname: Sousa
authors.forename: Valeska L
authors.initials: VL
authors.lastname: Andreozzi
authors.forename: Marília
authors.initials: M
authors.lastname: Antunes
authors.forename: Maria A
authors.initials: MA
authors.lastname: Amaral-Turkman
authors.forename: Helena
authors.initials: H
authors.lastname: Canhão
authors.forename: Ana F
authors.initials: AF
authors.lastname: Mourão
authors.forename: Joana
authors.initials: J
authors.lastname: Lopes
authors.forename: Joana
authors.initials: J
authors.lastname: Caetano-Lopes
authors.forename: Pamela
authors.initials: P
authors.lastname: Weinmann
authors.forename: Marta
authors.initials: M
authors.lastname: Sobral
authors.forename: Patrícia
authors.initials: P
authors.lastname: Nero
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Saavedra
authors.forename: Armando
authors.initials: A
authors.lastname: Malcata
authors.forename: Margarida
authors.initials: M
authors.lastname: Cruz
authors.forename: Rui
authors.initials: R
authors.lastname: Melo
authors.forename: Araceli
authors.initials: A
authors.lastname: Braña
authors.forename: Luis
authors.initials: L
authors.lastname: Miranda
authors.forename: José V
authors.initials: JV
authors.lastname: Patto
authors.forename: Anabela
authors.initials: A
authors.lastname: Barcelos
authors.forename: José Canas
authors.initials: JC
authors.lastname: da Silva
authors.forename: Luís M
authors.initials: LM
authors.lastname: Santos
authors.forename: Guilherme
authors.initials: G
authors.lastname: Figueiredo
authors.forename: Mário
authors.initials: M
authors.lastname: Rodrigues
authors.forename: Herberto
authors.initials: H
authors.lastname: Jesus
authors.forename: Alberto
authors.initials: A
authors.lastname: Quintal
authors.forename: Teresa
authors.initials: T
authors.lastname: Carvalho
authors.forename: José A Pereira
authors.initials: JA
authors.lastname: da Silva
authors.forename: Jaime
authors.initials: J
authors.lastname: Branco
authors.forename: Mário Viana
authors.initials: MV
authors.lastname: Queiroz
mesh_terms: D017668:Age of Onset; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000503:physiopathology*; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007596:Joints / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D019637:Orthopedic Procedures; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018582:Sick Leave; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D014409:Tumor Necrosis Factor-alpha