TNF-α gene polymorphisms in Type 1 (insulin-dependent) diabetes mellitus View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1989-07

AUTHORS

K. Badenhoop, G. Schwarz, J. Trowsdale, V. Lewis, K. H. Usadel, E. A. M. Gale, G. F. Bottazzo

ABSTRACT

Type 1 (insulin-dependent) diabetes mellitus, like some other autoimmune diseases, is linked to certain alleles coded by genes in the HLA-D region. Sequence analysis of DQ beta chains indicates that aspartic acid at codon 57 confers resistance to the development of Type 1 diabetes. However, a full explanation for the HLA-association of Type 1 diabetes, particularly the increased susceptibility of DR3/4 heterozygotes is still awaited. The localisation of tumour necrosis factor genes on the short arm of chromosome 6 between HLA-B and the complement genes (Class III) prompted us to investigate a possible polymorphism of TNF-alpha at the genomic level in relation to Type 1 diabetes susceptibility. A dialleleic TNF-alpha restriction fragment length polymorphism was found with Ncol and its segregation with HLA-haplotypes analysed in diabetic families. We describe here a strong linkage of TNF-alpha alleles with certain DR haplotypes. For example, the common extended haplotype HLA A1-B8-DR3 was almost exclusively associated with the 5.5 kb TNF-alpha allele whereas Bw62-DR4 with the 10.5 kb allele. Thus both alleles segregate to diabetic patients. DR matched haplotypes of affected family members differed significantly from those of the non-affected at the TNF alpha locus. All affected sibling pairs in 11 multiplex affected families were identical for TNF-alpha alleles, even if they were only haploidentical for HLA-B-DR haplotypes. In addition, heterozygosity for the TNF-alpha alleles was significantly more frequent in the patients. This tight linkage of TNF-alpha alleles with some extended haplotypes could help to explain the HLA-association of Type 1 diabetes as well as some other autoimmune diseases. More... »

PAGES

445-448

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf00271265

DOI

http://dx.doi.org/10.1007/bf00271265

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1050838135

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/2572498


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