Nco I Restriction Fragment Length Polymorphism (RFLP) of the Tumor Necrosis Factor (TNFα) region in four autoimmune diseases

Abstract

The two-allele NcoI Restriction Fragment Length Polymorphism (RFLP) of the TNF alpha region yielding bands of 5.5 and 10.5 kb was investigated in patients with systemic lupus erythematosus (SLE), pauciarticular juvenile rheumatoid arthritis (P-JRA), rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). In all four disease, we found a decreased frequency of the 10.5 kb allele which, however, was significant only in the SLE group. In all conditions except RA, the frequency of the 5.5 kb fragment was increased. In pSS and SLE, the frequency of HLA-B8 was increased in 5.5 kb fragment positive patients compared with corresponding controls and thus, the increase of this band and the decrease of the 10.5 kb band may be secondary to HLA-B8 associations owing to strong positive linkage disequilibrium between HLA-B8 and the 5.5 kb band.

Effects of Tumor Necrosis Factor Gene Polymorphisms on Patients With Congestive Heart Failure

“…TNF genotypes in each population are summarized in the Table. The observed allele frequencies were similar to those reported in the previous studies, 8,[11][12][13][14][15] and no differences were found between CHF and controls: TNFA1/TNFA2ϭ0.84/ 0.16 (CHF) or 0.84/0.16 (control) and TNFB1/TNFB2ϭ0.33/ 0.67 (CHF) or 0.32/0.68 (control). Furthermore, there were no differences in functional classes, ejection fraction, or cause of CHF by TNFA or TNFB genotypes (data not shown).…”

“…9,12 The frequency of the TNFA2 allele increases in rheumatoid arthritis and systemic lupus erythematosus, 13 and homozygotes for the TNFA2 allele have a higher risk for death due to cerebral malaria. 14 In contrast, the TNFB2 allele decreases in systemic lupus erythematosus, 15 and homozygotes for the TNFB2 allele in severe sepsis have a higher mortality rate with higher circulating levels of TNF-␣. 11 Given the importance of TNF-␣ in the pathogenesis of CHF, we hypothesized that these genetic variations might affect susceptibility to and severity of CHF.…”

Cytokine Polymorphisms in Systemic Lupus Erythematosus and Sjögren's Syndrome

“…In this population, the 2 308 allele was found to be associated to SLE on its own, independent of the DR3 type [45]. A NcoI Restriction-Fragment Length Polymorphism (RFLP) was first believed to be located in the TNF-a region [47,48], but was later mapped to the first intron of the TNF-b gene [49,50]. The TNFB*1 allele carries the NcoI site, while TNFB*2 does not, owing to a point mutation.…”

“…Studies in the mouse have indicated that a low production of TNF-a may be involved in the pathogenesis of autoimmune lupus nephritis, and that an RFLP in the TNF-a gene correlated with a reduced level of TNF-a [73]. The NcoI RFLP polymorphisms discussed in connection with SLE, have also been investigated for association to primary SS [48]. A decreased frequency of the TNFB*2 allele was found, but notably, was not significant in SS, only in SLE.…”

Extensive genetic polymorphism in the human tumor necrosis factor region and relation to extended HLA haplotypes

“…This hypothesis has been difficult to test because of a lack of genetic markers in the locus: an extensive search for restriction fragment length polymorphisms (RFLPs) has yielded a biallelic Nco I RFLP (10-13) and a very rare EcoRI RFLP (14). In spite of its limited information content, the Nco I RFLP has already allowed some tentative associations between TNF alleles and autoimmune diseases (11,15); recent evidence also suggests that one Nco I allele correlates with increased TNF-a and reduced TNF-13 production (13,16).…”