Comparative analysis of the genetic associations of HLA-DR3 and tumour necrosis factor alpha with human IDDM.
Insulin-dependent diabetes mellitus (IDDM) is associated with class II molecules of the MHC on chromosome 6, in particular HLA-DR and -DQ alleles, but a pathogenic role for TNF-alpha in the class III region of the MHC has also been implied. We therefore tested whether there was any independent association between a biallelic TNF polymorphism and IDDM. The TNF2 allele was present in 61 of 114 (54%) IDDM patients compared to 101 of 253 (40%) control subjects (odds ratio 1.73; p < 0.02). Stratification analysis in individuals matched for HLA-DR3 revealed, however, that this association was not independent of HLA-DR3 and is most likely to be a result of linkage disequilibrium between these alleles.
Cox
A
A
Department of Medicine and Pharmacology, University of Sheffield, Royal Hallamshire Hospital, UK.
Gonzalez
A M
AM
Wilson
A G
AG
Wilson
R M
RM
Ward
J D
JD
Artlett
C M
CM
Welsh
K
K
Duff
G W
GW
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005787:Gene Frequency; D005838:Genotype; D015798:HLA-DR1 Antigen / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D008969:Molecular Sequence Data; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D017931:DNA Primers; D015798:HLA-DR1 Antigen; D015803:HLA-DR3 Antigen; D014409:Tumor Necrosis Factor-alpha