Tumour necrosis factor microsatellites in reactive arthritis (original) (raw)
Related papers
Annals of the Rheumatic Diseases, 2001
Objective-To study the association between rheumatoid arthritis (RA) and HLA and tumour necrosis factor (TNF) polymorphism in Peruvian mestizo patients in comparison with ethnically similar controls. Methods-Seventy nine patients with RA and 65 ethnically matched healthy controls were genotyped for HLA-DRB1, HLA-DQA1, HLA-DQB1, and TNF and TNF alleles using PCR amplification. Clinical severity was assessed as mild, moderate, or severe in 35 of the patients. Results-TNF 6 showed the strongest association with disease susceptibility. The TNF 6 allele was more common in patients than in controls (p<0.0076) and the proportion of patients with at least one copy of this allele was greater (p<0.015, relative risk 2.35). Among the HLA-DRB1* alleles with the shared epitope sequence, only the DRB1*1402 allele was significantly increased in patients compared with controls (p<0.0311), as was the proportion of patients with at least one copy of this allele (p<0.0232, relative risk 2.74). In contrast, the overall frequency of alleles with the shared epitope was not diVerent in patients and controls. The haplotype HLA-DRB1*1402-DQB1*0301-DQA1*0401 was significantly more common in patients. TNF 6 was more common in patients whether or not they had this haplotype. None of the 11 patients lacking the TNF 6 allele had severe disease. Conclusions-This study shows for the first time that TNF gene polymorphism is associated with susceptibility to RA in a non-white population. TNF 6 and HLA-DRB1*1402 independently conferred significantly increased risk in Peruvian mestizo patients.
International Journal of Immunogenetics, 2011
The objective was to analyze the possible involvement of tumour necrosis factor-alpha (TNF-a) )308 G ⁄ A promoter polymorphism in the susceptibility and ⁄ or the disease profile of rheumatoid arthritis (RA) in Egyptian patients. TNF-a )308 G ⁄ promoter polymorphism detection by amplification refractory mutation system (ARMS) technique was carried out for 122 RA patients and 120 healthy controls. TNF-a )308 G allele ⁄ GG homozygous genotype were higher in patients with rheumatoid arthritis than those in control group (P < 0.001, respectively). A statistically significant association was found between the frequency of the A allele and presence of erosion (OR = 3.42, P = 0.015). No associations were found between the distribution of TNF-a )308 G ⁄ A alleles ⁄ genotypes and age of patients, disease duration, absence of remission, presence of deformity, clinical manifestations of the disease and presence or absence of rheumatoid factor. The positivity of rheumatoid factor was associated with occurrence of erosion (OR = 25.0, P < 0.001). The results of this study demonstrate the association of the TNF-a )308 G allele and GG homozygous genotype with susceptibility to RA and the A allele with the presence of erosion in the Egyptian patients.
Genomics, 2001
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with a multifactorial genetic basis. However, pathogenic genes for RA other than the human leukocyte antigen (HLA)-DRB1 gene have yet to be identified. Here, we investigated whether there is a second susceptibility locus for RA within the human major histocompatibility complex using 18 microsatellite markers distributed from the centromeric (HSET) to the telomeric end (P5-15) of the 3.6-Mb HLA region. Statistical studies of associated alleles on each microsatellite locus showed that one pathogenic gene for RA in the HLA region is localized in the DRB1 gene, as expected. Further, a second susceptibility gene of RA was suggested to be present in the HLA class III region, narrowed to 70 kb, that is just telomeric of the TNF gene cluster (TNFA and LTA) and that is located between the microsatellites TNFa and C1-2-A. In this critical segment, four expressed genes have been thus far identified, NFKBIL1 (IkappaBL), ATP6G, BAT1, and MICB, all of which are candidate genes for determining susceptibility to RA. These results exclude the possibility of involvement of the TNFA genes (TNF-alpha) in the development of RA, which was suggested previously to be a strong candidate for RA in the class III region.
2003
Objective. To investigate the association of the 2308 polymorphism in the promoter region of the tumour necrosis factor (TNF) gene with susceptibility to the development of RA. We also explored the expression and cytotoxicity of TNF in relation to the 2308 polymorphism. Methods. We recruited 92 RA patients and 42 healthy control subjects. Genotyping for the TNF promoter was performed by polymerase chain reaction– restriction fragment length polymorphism analysis. To study the overexpression of TNF we used a whole-blood culture system. TNF cytotoxicity was assessed in the L929 cell line. Results. The TNF2 allele was found in 23% of RA patients and 10% of controls. Although both groups showed high variability in serum TNF concentration, in the lipopolysaccharide-induced TNF level and in the cytotoxicity of the cytokine in the L929 cell line, these differences were not associated with the 2308 TNF polymorphism. Conclusion. No associations were found between the 2308 TNF promoter polymo...
A tumour necrosis factor alpha polymorphism is not associated with rheumatoid arthritis
Annals of the Rheumatic Diseases, 1995
Objective-To determine whether a polymorphism within the tumour necrosis factor a (TNFa) gene is associated with susceptibility to, or severity of, rheumatoid arthritis (RA). Methods-Consecutive patients with recent onset RA were enrolled in a prospective trial. DNA was collected, disease activity was measured at presentation, and radiographic progression at three years was assessed. Typing of TNFa was by polymerase chain reaction and single stranded conformation polymorphism analysis. Results-No association of TNFa alleles and susceptibility to, or severity of, RA was demonstrated. Conclusions-These results indicate that this TNFa polymorphism does not play a part in the genetic background of RA.
Some disease-associated ancestral haplotypes carry a polymorphism of TNF
Human Immunology, 1989
We describe here an Nco I restriction fragment length polymorphism of tumor necrosis factor carried by the 8.1 (HLA-A1,B8,BfS,C4AQO,C4B1,DR3) and the 44.l (HLA-B44,BfS, C4A3, C4BQO, DR4) ancestral haplotypes associated with complications of rheumatoid arthritis. By examining multiple examples of these and other ancestral haplotypes it was seen that 8.1 and 44.1 ancestral haplotypes yield fragments of approximately 5.5 kb while many other ancestral haplotypes carry fragments of approximately 10.5 kb. The polymorphism is associated with the ancestral haplotype rather than the HLA-B or -DR allele defined by conventional serology. ABBREVIATIONS