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Analysis of tumor necrosis factor-a promoter polymorphism in type 1 diabetes: HLA-B and -DRB1 alleles are primarily associated with the disease in Japanese.
- Source :
-
Tissue Antigens . Jan2000, Vol. 55 Issue 1, p10-16. 7p. 1 Diagram, 2 Charts. - Publication Year :
- 2000
-
Abstract
- Polymorphisms in the 5-flanking region of the tumor necrosis factor (TNF)-α gene were examined to study the genetic background of type 1 diabetes in Japanese. Five different biallelic polymorphisms were examined in 136 type 1 diabetic patients and 300 control subjects. The frequencies of individuals carrying TNF-α-857T allele (designated as TNFP-D allele) or -863A/-1,031C allele (designated as TNFP-B allele) were significantly increased in the patients as compared with the controls. Since these TNF-α alleles are in linkage disequilibria with certain DRB1 and HLA-B alleles, two-locus analyses were carried out. The TNFP-D allele did not increase the risk in either the presence or absence of the DRB1∗0405 or HLA-B54 allele, while the DRB1∗0405 and HLA-B54 alleles per se could confer susceptibility in both the TNFP-D allele-positive and -negative populations. Moreover, an odds ratio was remarkably elevated in the population carrying both DRB1∗0405 and HLA-B54. Similarly, the TNFP-B allele did not show significant association with the disease in either the HLA-B61-positive or -negative population, while the HLA-B61 allele could significantly increase the risk in the TNFP-B allele-positive population. These data suggest that the associations of TNFP-D and -B alleles may be secondary to their linkage disequilibria with the susceptible HLA class I and class II alleles. Because HLA-B and DRB1 genes were independently associated, both of these genes may be contributed primarily to the pathogenesis of type 1 diabetes in Japanese. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TUMOR necrosis factors
*GENETIC polymorphisms
*CELL-mediated cytotoxicity
Subjects
Details
- Language :
- English
- ISSN :
- 00012815
- Volume :
- 55
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Tissue Antigens
- Publication Type :
- Academic Journal
- Accession number :
- 5862994
- Full Text :
- https://doi.org/10.1034/j.1399-0039.2000.550102.x