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TNF microsatellites polymorphism is associated with rheumatoid arthritis. Confirming evidence in northwestern Colombians

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Gomez L.M.
Ruiz-Narváez E.A.
Pineda-Tamayo R.
Rojas-Villarraga A.
Anaya, Juan-Manuel

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2007

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Abstract
Objective: To examine the contribution of tumor necrosis factor alpha (TNF) microsatellite (a to e) polymorphism to the genetic risk of developing rheumatoid arthritis (RA) in a northwestern Colombian population. Methods: This was an association study in which 108 RA patients and 222 matched individuals were enrolled. HLA-DRB1 and DQB1 polymorphisms were evaluated to examine for linkage disequilibrium between these loci and TNF microsatellites. Genotyping was performed using denaturing polyacrylamide gels and polymerase chain reaction-sequence techniques. Results: By unconditional logistic regression analysis, the TNFa6 allele (OR= 2.37, 95%CI 1.07-5.24) and the TNFb4 allele (OR= 3.01, 95%CI 1.07-9.00) were observed to be associated with disease. These associations were independent of HLA-DR and HLA-DQ since linkage disequilibrium between HLA class II and TNF microsatellites was not observed. In addition, patients with the TNFa8 allele had a five times greater risk of developing extra-articular manifestations as compared to patients without this allele (OR = 5.07, 95%CI 1.14-22.52), regardless of age and the duration of disease. Haplotype analysis disclosed a protective effect for TNFa7/b7/c1/d4/e3/-308G/-238G. Conclusion: These results confirm that the TNF locus exerts a primary influence on both susceptibility to and the severity of RA. © Copyright Clinical and Experimental Rheumatology 2007.
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Cytokine , rheumatoid , genetic , Hla antigen class 2 , Hla dqb1 antigen , Hla dr antigen , Tumor necrosis factor , Tumor necrosis factor 238g , Tumor necrosis factor 308g , Tumor necrosis factor a6 , Tumor necrosis factor a7 , Tumor necrosis factor a8 , Tumor necrosis factor alpha , Tumor necrosis factor b4 , Tumor necrosis factor b7 , Tumor necrosis factor c1 , Tumor necrosis factor d4 , Tumor necrosis factor e3 , Unclassified drug , Adult , Age distribution , Allele , Article , Clinical feature , Colombia , Confidence interval , Controlled study , Disease duration , Disease severity , Female , Gene frequency , Gene linkage disequilibrium , Gene locus , Gene sequence , Genetic association , Genetic polymorphism , Genetic risk , Genetic susceptibility , Genotype , Haplotype , Human , Logistic regression analysis , Major clinical study , Male , Polymerase chain reaction , Priority journal , Protein function , Rheumatoid arthritis , Sequence analysis , Single nucleotide polymorphism , Adult , Arthritis , Colombia , Female , Genetic predisposition to disease , Humans , Linkage disequilibrium , Male , Microsatellite repeats , Middle aged , Polymorphism , Regression analysis , Risk factors , Severity of illness index , Tumor necrosis factor-alpha , Genetic , Hla , Latin america , Microsatellites , Rheumatoid arthritis , Tnf
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