Tumour Necrosis Factor‐β Gene RFLP Alleles in Finnish IDDM Hapiotypes

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Abstract
The genes located between class II and class I HLA genes including polymorphic tumour necrosis factor (TNF) genes may contribute to the disease susceptibility in IDDM. Restriction fragment polymorphisms of the TNF‐β gene have been found to be fixed in the major IDDM susceptibility haplotypes, the B62,DR4 haplotype being associated with the 10.5‐kb fragment and the B8,DR3 haplotype with a 5.5‐kb fragment. We studied this TNF polymorphism in a sample of diabetic families. In all IDDM‐associated haplotypes (n= 129) the 5.5‐kb allele was more frequent than in haplotypes found only in healthy family members (n=112) (58.1% versus 40.2%, Pn= 63) did not differ from that expected according to the Hardy‐Weinberg distribution. Our results indicate that the 10.5‐kb allele of TNF‐β gene as such is not a risk factor contributing to DR4/DQ8‐associated susceptibility. Alternatively, there may be heterogeneity in pathogenetic effector mechanisms.