Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus.

Jacob, Chaim O.; Fronek, Zdenka; Lewis, Gail D.; Koo, May; Hansen, John A.; McDevitt, Hugh O.

doi:10.1073/pnas.87.3.1233

Cited by 595 publications

(316 citation statements)

References 22 publications

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“…Sequences within the 1,100bp stretch of DNA between the 3' end of the adjacent lymphotoxin-α gene and the first exon of the TNF gene are central in the control of transcription [7,8]. Production of TNF shows stable inter-individual variation [9] and alleles of the TNF promoter have been correlated with levels of gene expression [10,11].…”

Section: Introductionmentioning

confidence: 99%

Age-related loss of CpG methylation in the tumour necrosis factor promoter

et al. 2011

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Background: Dysregulated production of TNF has been implicated in the pathogenesis and severity of inflammatory rheumatic diseases, many of which show age-related increased incidence. Ageing is also associated with changes in the immune system including higher systemic levels of pro-inflammatory cytokines.Methylation of DNA is an important regulator of gene expression and changes with age.Objective: In this study we investigated whether the DNA methylation status of the TNF promoter changed with age in peripheral blood leukocytes and macrophages. Methods and results:Using pyrosequencing assays we detected age-related demethylation of CpG motifs (-304, -245 and -239) Conclusions: These data suggest a potential role of accrued changes in DNA methylation in the development of age-related inflammatory diseases, such as rheumatoid arthritis and polymyalgia rheumatica, in which TNF is a pivotal mediator.3

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Section: Introductionmentioning

confidence: 99%

Age-related loss of CpG methylation in the tumour necrosis factor promoter

et al. 2011

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“…The level of TNF-expression has been correlated with the HLA genotype, in particular HLA-DR alleles and with polymorphic sequences closely linked to the TNF-locus: namely, the NcoI restriction fragment length polymorphism (RFLP) in the first intron and microsatellites within the first intron or the upstream region of the TNF-gene [4,5]. These findings suggest that TNF-expression depends on polymorphic variations in linkage disequilibrium with the above HLA marker.…”

Section: Introductionmentioning

confidence: 99%

Tumour necrosis factor-alpha (TNF-α) gene polymorphism and expression in pre-eclampsia

Chen

Wilson²,

Wang

et al. 1996

Clinical and Experimental Immunology

156

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SUMMARYPre-eclampsia is an endothelial disorder and TNF-has fundamental effects on endothelial cells by several means, including altering the balance between oxidant and anti-oxidant, changing the pattern of prostaglandin production and affecting expression of several cell surface components. To determine whether TNF-mRNA expression is increased in pre-eclamptic patients, leucocytes from pre-eclamptic patients, normal pregnant women and normal non-pregnant women were studied for TNF-expression using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Using a model of 373A ABI Sequencer, TNF-gene polymorphism was also analysed by GENESCAN and Genotyper software in order to explain the mechanism of abnormal TNF-expression. Our results show that TNFmRNA expression is significantly elevated in pre-eclamptic patients compared with the other two control groups. The high expression of TNF-may be associated with the TNF1 allele, whose frequency is markedly increased in pre-eclamptic patients. These observations are consistent with a major role for TNF-in mediating endothelial disturbances, and suggest a key role for TNF-in the development of pre-eclampsia.

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“…The strong linkage disequilibrium among the Ͼ200 genes of the MHC has made it challenging to delineate the specific contribution of individual MHC genes to the pathogenesis of RA (19)(20)(21). Increased production of TNF␣ has been demonstrated in DR3ϩ and DR4ϩ individuals as compared with DR2ϩ individuals, suggesting genetic variation in levels of TNF␣ production (22). RA is associated with cytokine network dysfunction (23), particularly TNF␣, which mediates a broad range of proinflammatory and immunostimulatory activities (24).…”

mentioning

confidence: 99%

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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Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus.

Cited by 595 publications

References 22 publications

Age-related loss of CpG methylation in the tumour necrosis factor promoter

Age-related loss of CpG methylation in the tumour necrosis factor promoter

Tumour necrosis factor-alpha (TNF-α) gene polymorphism and expression in pre-eclampsia

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

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