TNF microsatellites polymorphism is associated with rheumatoid arthritis. Confirming evidence in north-western Colombians

CER3030
2007 Vol.25, N°3
PI 0443, PF 0448
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PMID: 17631742 [PubMed]

Abstract

OBJECTIVES:
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 micro- satellites. 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.
CONCLUSIONS:
These results confirm that the TNF locus exerts a primary influence on both susceptibility to and the severity of RA.