Tumor necrosis factor alpha-308 and -238 polymorphisms in rheumatoid arthritis. Association with messenger RNA expression and sTNF-alpha.
BACKGROUND
Rheumatoid arthritis (RA) is characterized by a progressive joint damage mediated mainly by tumor necrosis factor alpha (TNFalpha). We investigated the relationship of TNFalpha-308 and -238 polymorphisms with messenger RNA (mRNA) expression and soluble TNFalpha (sTNFalpha) in 50 RA and 100 healthy subjects (HS).


METHODS
Clinical and laboratory assessments were performed. Spanish Health Assessment Questionnaire Disability Index, Spanish version of Arthritis Impact Measurement Scales and Disease Activity Score using 28 joint count indices were applied to RA patients. The TNFalpha-308 and -238 polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism techniques. The mRNA expression of TNFalpha was quantified by real-time polymerase chain reaction. The sTNFalpha levels were measured by enzyme-linked immunosorbent assay.


RESULTS
The TNFalpha-308 polymorphism showed an increased frequency of guanine (G)/adenine (A) genotype in RA versus HS (P = 0.03; 95% confidence interval, 1.05-8.08; odds ratio, 2.9) and also the A allele was more frequent in RA patients versus HS (P = 0.04; 95% confidence interval, 1.01-7.29; odds ratio, 2.7). The G/G genotype and also the G allele were more frequent in HS. No significant difference was observed in TNFalpha-238 polymorphism. Rheumatoid arthritis patients showed high TNFalpha mRNA expression (1.33-fold). The G/G genotype was associated with high mRNA and sTNFalpha levels in both TNFalpha polymorphisms. The correlation of sTNFalpha levels with C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, Spanish Health Assessment Questionnaire Disability Index, and Spanish version of Arthritis Impact Measurement Scales, was observed.


CONCLUSIONS
The TNFalpha-308 polymorphism is a susceptibility marker to RA. The G/G genotype is associated with a high mRNA and soluble TNFalpha expression.
Oregón-Romero
Edith
E
Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México.
Vázquez-Del Mercado
Mónica
M
Ruiz-Quezada
Sandra Luz
SL
Navarro-Hernández
Rosa Elena
RE
Rangel-Villalobos
Héctor
H
Martínez-Bonilla
Gloria
G
Bernard-Medina
Ana Guilaisne
AG
Armendáriz-Borunda
Juan
J
García-Bañuelos
Jesús
J
Muñoz-Valle
José Francisco
JF
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000235:genetics*
D017931:DNA Primers; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha