Fas promoter -670 polymorphism is associated with development of anti-RNP antibodies in systemic lupus erythematosus.

OBJECTIVE To evaluate whether the polymorphism of Fas promoter -670 is associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and their clinical features. METHODS A polymerase chain reaction of a genomic DNA-restriction fragment length polymorphism was used to determine genotypes of the Fas promoter -670 in 87 patients with SLE, 87 with RA, and 87 healthy controls. A second cohort of SLE patients (n = 85) was included. Clinical manifestations were analyzed in each patient and correlated with the genotypes. RESULTS The genotype distribution of the Fas promoter -670 did not differ between patients with SLE and control subjects (AA, GA, GG genotypes 31, 54, 15% vs 30, 55, 15% controls, respectively; chi-squared = 0.03, 2 df, p = 0.99) and between RA patients and controls (AA, GA, GG genotypes 38, 44, 18% vs 30, 55, 15% controls, respectively; chi-squared = 2.30, 2 df, p = 0.32). Regarding the clinical status of lupus patients according to Fas promoter -670 genotypes, there was no significant difference in age at onset, anti-dsDNA titer, C3, C4 level, renal involvement, number of American College of Rheumatology (ACR) criteria met, SLE Disease Activity Index, SLE International Collaborating Clinics/ACR Damage Index, or autoantibody profiles. However, the frequency of anti-RNP antibody was significantly different in the AA, GA, and GG groups (71, 25, 30%; chi-squared = 13.29, 2 df, p = 0.001). To confirm this finding, the Fas promoter -670 genotype was examined in a second cohort of SLE patients (n = 85). The result in the second cohort replicated the association shown in the first. In patients with RA, there was no significant difference in clinical and laboratory findings according to the Fas promoter -670 genotypes. CONCLUSION Our data suggest that the Fas promoter -670 polymorphism is associated with development of anti-RNP antibodies in SLE.

[1]  J. Lanchbury,et al.  A Fas promoter polymorphism at position -670 in the enhancer region does not confer susceptibility to Felty's and large granular lymphocyte syndromes. , 1999, Rheumatology.

[2]  J. Edmonds,et al.  Evaluation of a new Apo-1/Fas promoter polymorphism in rheumatoid arthritis and systemic lupus erythematosus patients. , 1999, Rheumatology.

[3]  N. Manolios,et al.  Identification and characterization of polymorphisms in the promoter region of the human Apo-1/Fas (CD95) gene. , 1997, Molecular immunology.

[4]  S. Nagata,et al.  Apoptosis by Death Factor , 1997, Cell.

[5]  P. Emery,et al.  Inhibition of T cell apoptosis in the rheumatoid synovium. , 1997, The Journal of clinical investigation.

[6]  D. Symmons,et al.  The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. , 1996, Arthritis and rheumatism.

[7]  F. Ramsdell,et al.  Fas and FasL in the homeostatic regulation of immune responses. , 1995, Immunology today.

[8]  D. Sackett,et al.  Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. , 1992, Arthritis and rheumatism.

[9]  R. Chang,et al.  The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. , 1992, Arthritis and rheumatism.

[10]  M. Liang,et al.  The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. , 1988, Arthritis and rheumatism.

[11]  J F Fries,et al.  The 1982 revised criteria for the classification of systemic lupus erythematosus. , 1982, Arthritis and rheumatism.

[12]  A. Silman,et al.  Investigation of candidate disease susceptibility genes in rheumatoid arthritis: principles and strategies. , 1997, The Journal of rheumatology.