Tumor necrosis factor gene polymorphisms in ankylosing spondyiitis

Abstract

Despite the strength of the association of ankylosing spondylitis (AS) with HLA-BZ7, other genetic elements could play a possible role in the pathophysiology of AS. In view of its gene location, in the proximity of the HLA-B locus, and biological effects, tumor necrosis factor genes are potential candidates for additive susceptibility factors to AS. TNFa and TNFP genotypes were analyzed by PCR-RFLP in 57 patients with AS, 102 random controls and 30 HLA-B*27-positive controls. No significant differences of TNFa promoter variations at position -308 and -238 were found in AS patients in comparison with controls. The -244 polymorphism was notdetected in our population. The TNFP genotype frequency was significantly different between AS patients and random controls. However, when the distribution of the TNFP genotype was compared in B*27-positive AS patients and controls, these differences disappeared. In addition, we demonstrated that the TNFP*1 was in strong linkage disequilibrium with the B*27 allele, which may explain the differences observed for the TNFP genotype among AS patients and random controls. Our data suggest that the polymorphisms of TNFa and TNFP genes do not have an independent effect on AS susceptibility.

Polymorphisms of tumor necrosis factor-α promoter region for susceptibility to HLA-B27-positive ankylosing spondylitis in Korean population

“…unrelated healthy controls (P \ 0.03). In contrast, other studies from three different European populations demonstrated that polymorphisms at positions -308, -238, and -376 of the TNF-a gene had no effect on susceptibility to AS [15][16][17]. Among these studies, Kaijzel et al identified a significant difference in the -238A allele between HLA-B27 ?…”

“…AS patients classified by clinical subtypes and controls, n the pathogenesis of AS [11,12]. Several studies have attempted to investigate the relationship between susceptibility to AS and TNF-a polymorphisms in patients with AS [13][14][15][16][17][18][19]. However, the results of these studies are inconsistent, most likely due to the use of diverse study populations.…”

“…However, other studies have failed to find differences in the frequencies of TNF-a promoter polymorphisms between patients with AS and control subjects comprising HLA-B27 -controls, random controls, or HLA-B27 ? individuals [15][16][17]. Recent studies of two different Asian samples found a close relationship between TNF-a polymorphisms and susceptibility to AS [18,19].…”

TNF-α promoter polymorphisms in sudden infant death

“…TNF␣-1031 TT 83 59 33 58 29 71 72 56 CT 50 35 22 39 11 27 52 41 C C 8 6 2 3 1 2 4 3 TNF␣-857 CC 122 85 47 84 35 90 106 82 CT 21 14 9 16 4 10 23 18 T T 1 1 0 0 0 0 0 Several studies have identified all nine polymorphisms in the TNF-␣ promoter region, some of which proved to have a functional effect on the transcription of the gene and TNF-␣ mRNA transcription [17,20 -22]. Several association studies link TNF-␣ polymorphism in the promoter region to various infectious and autoimmune diseases [23][24][25][26][27][28][29]. A functional analysis indicated that the 308/376 region is of no functional relevance to TNF transcription [30].…”

Genetics of Spondyloarthropathies and Inflammatory Bowel Disease: Searching for Common Susceptibility Factors

“…One report detected an association between -308 and AS [126]. No association was found among four promoter polymorphisms (located at c.-244, c.-376, c.-238 and c.-308) between AS and controls [127,128]. The CD-associated promoter polymorphisms have not been tested in SpA.…”