TNF promoter region allele frequencies in the White population and their expression levels (34.11)

Abstract

Abstract Tumor necrosis factor (TNF) is a pro-inflammatory cytokine that plays a variety of roles in immune regulation and disease. The TNF regulatory region contains numerous SNPs some of which affect expression. We previously identified nine alleles of TNF promoter region from random samples, but allele frequencies in different populations and diversity of the gene, as well as expression levels driven by the promoter alleles are not known. The TNF promoter and gene were sequenced from 82 random healthy White individuals. Three novel promoter alleles and two novel SNPs were identified. Novel SNPs also were found in intron 1 and the 3’ UTR. Promoter allele p*001 was the most common allele (55.49%). Allele p*002 (15.85%), p*006 (14.02%) and p*003 (7.32%) also were frequent, while all other alleles were found at less than 5% frequency. Differences were noted in an initial analysis of expression levels in T cells driven by the TNF promoter alleles. Allele p*004 was significantly increased in unstimulated and PMA/ionomycin conditions when compared to allele p*001. Expression was decreased for alleles p*005, p*006, and p*008 in comparison to allele p*001 in stimulated and unstimulated conditions. Allele p*007 showed decreased expression only in unstimulated conditions, while allele p*002 showed reduced expression only under stimulated conditions. These data confirm some of the previously reported impacts of SNPs on TNF expression and suggest an impact of additional SNPs on TNF levels.