NCOI Polymorphism within the TNFα Promotor Region and the First Intron of TNFβ Gene in Association with DRB1 Specificities in Healthy Volunteers

Abstract

TNFα and TNFβ polymorphism focused interest of several research groups — accordingly to the pivotal role of these cytokines in several inflammatory and autoimmune diseases and recent believe that TNF generation potential can be linked with genotype of these cytokines. PCR amplificats of the promoter region of TNFα gene as well as first intron region of TNFβ gene differ in human with respect to the sensitivity to NcoI digestion. When guanine is present in the position 308 (TNFαgene) or 1069 (TNFβ gene) NcoI digestion of PCR amplificats results with two products (pattern 1) but in the presence of adenine instead of guanine there is no break down products (pattern 2) [1,2]. These two patterns fulfill criteria of allelic specificities and constitute two alleles 1 and 2 in both TNFα and TNFβ genes (Table 1). TNFα and TNFβ genes are situated within the MHC complex in man [3,4]. This location may facilitate a link between TNF and HLA alleles. Several associations have been recently reported between TNFα alleles and diseases. Some of them, however, may be indirect, reflecting rather association with HLA antigens. Therefore, a study on linkage disequilibrium between TNFα, TNFβ and HLA alleles is desired. It has been already described that TNFα2 allele usually belongs to haplotype containing Al, B8 and DR3 genes [5]. In addition TNFα-308 genotype (TNFαl) is in a linkage with NcoI 5.5-kb RFLP of TNFβ gene (TNFβ2).

Table 1. Patterns of NcoI digestion seen in gel electrophoresis for TNFα and TNFβ alleles