Polymorphisms in the 5'-flanking region of tumor necrosis factor-alpha gene in patients with rheumatoid arthritis.

Polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor (TNF)-a gene were examined to study the genetic background of rheumatoid arthritis (RA). Four variant alleles, -1,031C/ -863A, -1,031C/-238A, -857T and -308A, were identified and examined in 387 RA patients and 575 healthy Japanese controls. The frequency of the -857T allele in RA patients was significantly higher than that in the controls. However, the HLA-DRB1 analysis in the same subjects showed that the DRB1*0405 allele, which is in linkage disequilibrium with the -857T, was more strongly associated with the disease susceptibility than the -857T allele. These results suggest that the susceptible gene to RA is more closely linked to the HLA-DRB1 locus than to the TNF-alpha locus.

[1]  D. Hartl,et al.  Identification of three new single nucleotide polymorphisms in the human tumor necrosis factor-alpha gene promoter. , 1998, Tissue antigens.

[2]  A. Kimura,et al.  Polymorphism of the 5′‐flanking region of the human tumor necrosis factor (TNF)‐α gene in Japanese , 1998 .

[3]  T. Ochi,et al.  The relationship between HLA-DRB1 alleles and disease subsets of rheumatoid arthritis in Japanese. , 1997, British journal of rheumatology.

[4]  F. Breedveld,et al.  Tumour necrosis factor alpha gene polymorphisms in rheumatoid arthritis: association with susceptibility to, or severity of, disease? , 1997, British journal of rheumatology.

[5]  H. Mcdevitt,et al.  Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[6]  R. Scorza,et al.  Association between polymorphisms in the TNF region and systemic lupus erythematosus in the Italian population. , 1996, Tissue antigens.

[7]  J. Blackwell,et al.  Polymorphism in tumor necrosis factor genes associated with mucocutaneous leishmaniasis , 1995, The Journal of experimental medicine.

[8]  J. Reveille,et al.  Most African-American Patients with Rheumatoid Arthritis Do Not Have the Rheumatoid Antigenic Determinant (Epitope) , 1995, Annals of Internal Medicine.

[9]  D. Kwiatkowski,et al.  Variation in the TNF-α promoter region associated with susceptibility to cerebral malaria , 1994, Nature.

[10]  J. Ghrayeb,et al.  Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. , 1993, Arthritis and rheumatism.

[11]  A. Cambon-Thomsen,et al.  Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF‐a and TNF‐0 by human mononuclear cells: a possible link to insulin‐dependent diabetes mellitus , 1993 .

[12]  D. Kioussis,et al.  Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. , 1991, The EMBO journal.

[13]  Paul Wordsworth,et al.  Polygenic susceptibility in rheumatoid arthritis. , 1991, Annals of the rheumatic diseases.

[14]  H. Mcdevitt,et al.  Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

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

[16]  P. Gregersen,et al.  The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. , 1987, Arthritis and rheumatism.

[17]  B. Woolf.  ON ESTIMATING THE RELATION BETWEEN BLOOD GROUP AND DISEASE , 1955, Annals of human genetics.

[18]  E. Pareja,et al.  Polymorphism at the TNF loci in rheumatoid arthritis. , 1997, Tissue antigens.

[19]  D. Grennan,et al.  Increased frequency of the uncommon allele of a tumour necrosis factor alpha gene polymorphism in rheumatoid arthritis and systemic lupus erythematosus. , 1995, Disease markers.

[20]  R. Winchester.  The molecular basis of susceptibility to rheumatoid arthritis. , 1994, Advances in immunology.