Contribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoter.
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.
Fonseca
João Eurico
JE
Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av, Professor Egas Moniz, 1649-028, Lisboa, Portugal. jefonseca@netcabo.pt
Cavaleiro
João
J
Teles
José
J
Sousa
Elsa
E
Andreozzi
Valeska L
VL
Antunes
Marília
M
Amaral-Turkman
Maria A
MA
Canhão
Helena
H
Mourão
Ana F
AF
Lopes
Joana
J
Caetano-Lopes
Joana
J
Weinmann
Pamela
P
Sobral
Marta
M
Nero
Patrícia
P
Saavedra
Maria J
MJ
Malcata
Armando
A
Cruz
Margarida
M
Melo
Rui
R
Braña
Araceli
A
Miranda
Luis
L
Patto
José V
JV
Barcelos
Anabela
A
da Silva
José Canas
JC
Santos
Luís M
LM
Figueiredo
Guilherme
G
Rodrigues
Mário
M
Jesus
Herberto
H
Quintal
Alberto
A
Carvalho
Teresa
T
da Silva
José A Pereira
JA
Branco
Jaime
J
Queiroz
Mário Viana
MV
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*
D005819:Genetic Markers; D014409:Tumor Necrosis Factor-alpha