Tumor necrosis factor receptor II gene polymorphism and severity of rheumatoid arthritis.
OBJECTIVE
The gene encoding tumor necrosis factor receptor type II (TNFRII) is a strong candidate in the pathogenesis of rheumatoid arthritis (RA). An association between a single-nucleotide polymorphism (196M/R) in exon 6 of the TNFRII gene and familial RA was recently reported. The present study was undertaken to test the hypothesis that there is an association between this polymorphism and the severity of RA.


METHODS
One hundred two white patients with early RA were included in this prospective study. The French version of the Health Assessment Questionnaire (F-HAQ) and a radiographic damage score (modified Sharp/van der Heijde method) were used to quantify the functional and structural severity of RA at baseline and after 4 years of followup. TNFRII 196M/R polymorphism genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis.


RESULTS
Among the 102 patients with RA, 63 (61.8%) were homozygous for the 196M allele, 36 (35.3%) were heterozygous for alleles 196M and 196R, and 3 (2.9%) were homozygous for the 196R allele. At baseline, the median radiographic and F-HAQ scores did not differ between RA patients who carried the 196R allele and those who did not. After 4 years of followup, the F-HAQ score was higher in RA patients carrying the 196R allele (median 1 [interquartile range (IQR) 0.125, 1.375]) than in noncarriers (0.375 [IQR 0, 1]) (P = 0.02), while the median radiographic score did not differ between RA patients who carried the 196R allele and those who did not.


CONCLUSIONS
The results of the present study support the hypothesis that there is an association between the TNFRII 196 M/R gene polymorphism and the functional severity of early RA.
Constantin
Arnaud
A
Centre Hospitalier Universitaire Rangueil, INSERM U558, and INSERM U563, Toulouse, France.
Dieudé
Philippe
P
Lauwers-Cancès
Valérie
V
Jamard
Bénédicte
B
Mazières
Bernard
B
Cambon-Thomsen
Anne
A
Cornélis
François
F
Cantagrel
Alain
A
D000328:Adult; D000368:Aged; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D001120:Arginine / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D001175:Arthrography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II; D012720:Severity of Illness Index
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D001120:Arginine; D008715:Methionine