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 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.
Gomez
L M
LM
Cellular Biology and Immunogenetics Unit, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia.
Ruiz-Narváez
E A
EA
Pineda-Tamayo
R
R
Rojas-Villarraga
A
A
Anaya
J-M
JM
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics*; D003105:Colombia; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha