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

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.

• Fecha de publicación: 2007
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/23670
• Acceso en línea: https://repository.urosario.edu.co/handle/10336/23670
• Palabra clave: Cytokine; 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; Colombia; Female; Genetic predisposition to disease; Humans; Linkage disequilibrium; Male; Microsatellite repeats; Middle aged; Regression analysis; Risk factors; Severity of illness index; Tumor necrosis factor-alpha; Genetic; Hla; Latin america; Microsatellites; Rheumatoid arthritis; Tnf; rheumatoid; genetic; Arthritis; Polymorphism
• License: Abierto (Texto Completo)