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TNF‐alpha GENE POLYMORPHISMS: ASSOCIATION WITH TYPE I (INSULIN‐DEPENDENT) DIABETES MELLITUS
Author(s) -
Badenhoop K.,
Schwarz G.,
Bingley P.,
Trowsdale J.,
Usadel K. H.,
Gale E. A. M.,
Bottazzo G. F.
Publication year - 1989
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/j.1744-313x.1989.tb00494.x
Subject(s) - type 2 diabetes mellitus , insulin , diabetes mellitus , medicine , gene , alpha (finance) , association (psychology) , tumor necrosis factor alpha , polymorphism (computer science) , type 2 diabetes , genetics , endocrinology , biology , allele , psychology , clinical psychology , construct validity , psychotherapist , psychometrics
SUMMARY The localization of TNF genes on the short arm of chromosome 6 between HLA B and the complement genes focused attention to that genetic region which harbours many immunologically relevant genes and is also thought to hold susceptibility genes for a variety of autoimmune diseases that are linked to specific alleles of particular loci in the HLA D region. Since the recently established HLA‐DR‐DQ variation accounts only for part of the genetic susceptibility to insulin‐dependent diabetes mellitus (IDDM) we searched for genomic variation of the tumour necrosis factor (TNF) alpha. We have identified a TNF‐alpha restriction fragment length polymorphism (RFLP) with N coI and analysed diabetic patients including their families, controls and homozygous typing cell lines (HTC) defined by the 10th International Histocompatibility Workshop. Segregation analysis in families and HTC results show a strong linkage of the TNF‐alpha 5.5 kb allele with DR types in particular with AIB8DR3 . This tight linkage of TNF‐alpha alleles with extended haplotypes and the significant increase of heterozygotes in patients could lead to some explanation of the DR3 association with a variety of autoimmune diseases particularly IDDM.