RGD Reference Report - Association of tumor necrosis factor and human leukocyte antigen DRB1 alleles with Graves' ophthalmopathy. - Rat Genome Database

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Association of tumor necrosis factor and human leukocyte antigen DRB1 alleles with Graves' ophthalmopathy.

Authors: Bednarczuk, T  Hiromatsu, Y  Seki, N  Ploski, R  Fukutani, T  Kurylowicz, A  Jazdzewski, K  Chojnowski, K  Itoh, K  Nauman, J 
Citation: Bednarczuk T, etal., Hum Immunol. 2004 Jun;65(6):632-9.
RGD ID: 7365073
Pubmed: (View Article at PubMed) PMID:15219383
DOI: Full-text: DOI:10.1016/j.humimm.2004.02.033

Tumor necrosis factor (TNF)-alpha plays a central role in the development of ophthalmopathy in patients with Graves' disease (GD). The aim of this study was to investigate the association of TNF promoter polymorphisms at positions -1031 (T-1031C), -863 (C-863A), -857 (C-857T), -308 (G-308A), and -238 (G-238A) with Graves' ophthalmopathy (GO). We studied the distribution of TNF and human leukocyte antigen (HLA) DRB1 alleles in 228 Polish white patients with GD, 106 of whom had ophthalmopathy (NOSPECS class > or = III) and 248 healthy subjects. TNF -308A and HLA-DRB1*03 alleles were significantly increased in patients with GD compared with healthy subjects. Stratification analysis revealed no independent association of -308A with GD when the DRB1*03 status was considered. Subdividing GD according to eye involvement revealed that the distribution of TNF promoter haplotypes differed significantly in patients with or without ophthalmopathy. The haplotype containing the -238A allele was absent in GO. The association of G-238A with GO was independent of DRB1 alleles. These results indicate that TNF G-308A is associated with susceptibility to GD (however, this association is not independent of HLA-DRB1*03) and that TNF G-238A is associated with the development of ophthalmopathy, suggesting that G-238A or a gene in linkage disequilibrium may be disease modifying in GD.

Disease Annotations    
Graves ophthalmopathy  (IAGP,ISO)
Graves' disease  (IAGP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
RT1-Db1  (RT1 class II, locus Db1)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
H2-Eb1  (histocompatibility 2, class II antigen E beta)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
HLA-DRB1  (major histocompatibility complex, class II, DR beta 1)
TNF  (tumor necrosis factor)

Additional Information