FUNCTIONAL-ANALYSIS OF A NEW POLYMORPHISM IN THE HUMAN TNF-ALPHA GENEPROMOTER

In this paper the functional relevance of a TNFA promoter polymorphism , a G/A polymorphic sequence at position -238, was tested by analysing its influence on TNF alpha production upon in vitro stimulation of mo nocytes from 78 healthy, unrelated individuals by lipopolysaccharide ( LPS) or after allogenic stimulation in a panel of 32 healthy individua ls. All TNFA-A positive individuals were either DR3 or DR7 positive, c onfirming the previously reported strong linkage disequilibrium of the TNFA-A allele with the two extended haplotypes (B18, F1C30, DR3) and (B57, SC61, DR7). No individuals homozygous for the TNFA-A allele were present in the panel. The mean level of TNF alpha production was not significantly different in TNFA-G/G homozygous and in TNFA-A/G heteroz ygous individuals after LPS stimulation of monocytes (P = 0.35) or aft er allogenic stimulation (P = 0.7). After LPS and allogenic stimulatio n DR3 positive individuals had a higher mean TNF production. This coul d not be further differentiated by typing for TNF -283.