NcoI restriction fragment length polymorphism (RFLP) of the tumour necrosis factor (TNF alpha) region in primary biliary cirrhosis and in healthy Danes

The restriction fragment length polymorphism of the human tumour necrosis factor (TNF alpha) region was investigated by means of 20 different restriction enzymes and a human TNF alpha cDNA probe. Only one of the enzymes, NcoI, revealed a polymorphic pattern consisting of fragments of 10.5 and 5.5 kb, which behaved as alleles. In a panel of 108 random, healthy, unrelated Danes, the phenotype frequencies of the 10.5 and 5.5 kb bands were 0.94 and 0.53 and the gene frequencies were 0.71 and 0.29, respectively. The test for Hardy-Weinberg equilibrium showed no significant deviation from the expected values. The 5.5 kb band was strongly positively associated with HLA-DR3, HLA-B8, and HLA-A1. In 22 patients with primary biliary cirrhosis a significantly (corrected P = 0.024) decreased frequency of the 10.5 kb fragment was found. Additional studies are in progress to substantiate this association.