Polymorphism at the TNF loci in rheumatoid arthritis

Vinasco, Javier; Beraún, Y.; Nieto, Antonio; Fraile, Aurora; Matarán, L.; Pareja, Eduardo; Martín, Javier

doi:10.1111/j.1399-0039.1997.tb02715.x

Cited by 113 publications

(79 citation statements)

References 31 publications

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“…For example, in a juvenile idiopathic arthritis cohort from Turkey, the -308 G-to-A polymorphism was associated with a poor clinical course (56). Vinasco et al (57) found more frequent nodular disease in their cohort of adult RA patients with the TNFA -308 AA plus AG genotypes. High levels of TNF␣ are associated with more severe disease in RA (58), and elevated levels of TNF␣ are found in the synovial fluid and synovial tissue of RA patients (25).…”

Section: Discussionmentioning

confidence: 89%

Association of tumor necrosis factor α polymorphism, but not the shared epitope, with increased radiographic progression in a seropositive rheumatoid arthritis inception cohort

Khanna

Park

et al. 2006

Arthritis & Rheumatism

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Objective. To determine whether the tumor necrosis factor ␣ (TNFA) -308 guanine-to-adenosine polymorphism and/or the shared epitope (SE) is associated with radiographic damage in patients with early rheumatoid arthritis (RA).Methods. The cohort consisted of 189 patients with early seropositive RA (median 5.6 months since symptom onset) who had active disease, no previous disease-modifying antirheumatic drug treatment, and >2 sets of scored radiographs of the hands/wrists and forefeet. TNFA -308 polymorphism was analyzed by polymerase chain reaction pyrosequencing. The SE was defined as presence of any 1 of the following HLA-DRB1 alleles: *0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001, *1402, or *1406. Radiographic progression was assessed by the total Sharp score.Results. Using a weighted least-squares regression analysis, patients with the -308 TNFA AA plus AG genotypes (n ‫؍‬ 49) had significantly higher rates of progression in erosion scores (median 0.84 versus 0.48 units/year), joint space narrowing (JSN) scores (0.42 versus 0.04), and total Sharp scores (1.70 versus 0.61) compared with patients with the TNFA GG genotype (n ‫؍‬ 140). Presence of the SE (n ‫؍‬ 137) was associated with significantly lower progression rates (per year) for total Sharp scores (median 0.9 versus 1.25 units/year) and JSN scores (0.04 versus 0.41), but not for erosion scores (0.50 versus 0.61) compared with patients without the SE (n ‫؍‬ 52). In a least-squares multiple linear regression model, the presence of the AA plus AG genotypes was associated with a significantly higher progression rate after adjusting for the presence of the SE, interaction between the SE and the AA plus AG genotypes, baseline log C-reactive protein level, Health Assessment Questionnaire Disability Index, total Sharp score, swollen joint count, and presence of osteophytes (osteoarthritis). There was a strong linkage disequili-

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Section: Discussionmentioning

confidence: 89%

Association of tumor necrosis factor α polymorphism, but not the shared epitope, with increased radiographic progression in a seropositive rheumatoid arthritis inception cohort

Khanna

Park

et al. 2006

Arthritis & Rheumatism

View full text Add to dashboard Cite

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“…24 Two subsequent Spanish studies also found no association between either À308 or À238 SNPs and susceptibility to RA. 25,26 A large study of Japanese RA patients (n ¼ 545) showed that while À308A was increased in RA patients, this increase was dependent on linkage to DRB1. 27 Another large Japanese study (n ¼ 387) looked at several TNF SNPs including À308, but only found that the T allele of the -857 SNP was increased in RA patients, and this link also proved to be dependent on HLA-DRB1*0405.…”

Section: Autoimmune Disease Associationsmentioning

confidence: 99%

Is there a future for TNF promoter polymorphisms?

2004

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The in vitro study of TNF promoter polymorphism (SNP) function was stimulated by the numerous case-control (association) studies of the polymorphisms in relation to human disease and the appearance of several studies claiming to show a functional role for these SNPs provided a further impetus to researchers interested in the role of TNF in their disease of interest. In this review we consider case-control studies, concentrating on the autoimmune and inflammatory diseases rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and asthma, and on infectious diseases including malaria, hepatitis B and C infection, leprosy and sepsis/septic shock. We also review the available evidence on the functional role of the various TNF promoter polymorphisms. In general, case-control studies have produced mixed results, with little consensus in most cases on whether any TNF polymorphisms are actually associated with disease, although results have been more consistent in the case of infectious diseases, particularly malaria. Functional studies have also produced mixed results but recent work suggests that the much studied À308G/A polymorphism is not functional, while the function of other TNF polymorphisms remains controversial. Studies of the TNF region are increasingly using extended haplotypes that can better capture the variation of the MHC region.

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“…[10][11][12][13] A major point of interest as to whether these cytokine markers can be related to human disease status 1,2,4-13 and studies in malignant 2 and autoimmune [4][5][6][7] disease have suggested that the TNF locus can contribute to disease susceptibility. Indeed, similar studies have demonstrated that IL-1 and IL-10 are also associated with the presence or severity of autoimmune diseases across a variety of ethnic backgrounds.…”

mentioning

confidence: 99%

“…While the majority of work in cytokine genetics has been carried out on the TNF locus, [2][3][4][5][6][7] other cytokines have also featured, notably IL-1 [8][9][10] and IL-10. [10][11][12][13] A major point of interest as to whether these cytokine markers can be related to human disease status 1,2,4-13 and studies in malignant 2 and autoimmune [4][5][6][7] disease have suggested that the TNF locus can contribute to disease susceptibility.…”

mentioning

confidence: 99%

Allele associations reveal four prominent haplotypes at the human interleukin-6 (IL-6) locus

et al. 2000

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We have examined four polymorphic elements in the human interleukin-6 (IL-6) locus and described their allele distribution in 73 unrelated, healthy individuals from the West-of-Scotland. These comprised three single nucleotide polymorphisms (SNP) in the 5Ј promoter region of the gene and one VNTR in the 3Ј region of IL-6. A statistical consideration of the relationship between alleles at each locus was carried out. Of a total of 12 possible haplotypes observed in the population, the analysis suggested that four were prominent. These accounted for 41.1%, 28.1%, 14.4% and 3.4% respectively; in total, 87% of the haplotypes present. Frequently, these proposed haplotypes were supported by homozygosity across all four loci within individuals. We propose that these haplotypes be identified as IL6.0103, IL6.0204, IL6.0207 and IL6.0307, in recognition of their frequency in this population and the alleles that they contain. Genes and Immunity (2000) 1, 451-455.

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Polymorphism at the TNF loci in rheumatoid arthritis

Cited by 113 publications

References 31 publications

Association of tumor necrosis factor α polymorphism, but not the shared epitope, with increased radiographic progression in a seropositive rheumatoid arthritis inception cohort

Association of tumor necrosis factor α polymorphism, but not the shared epitope, with increased radiographic progression in a seropositive rheumatoid arthritis inception cohort

Is there a future for TNF promoter polymorphisms?

Allele associations reveal four prominent haplotypes at the human interleukin-6 (IL-6) locus

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