Tumor necrosis factor promoter polymorphism TNF*-857 is a risk allele for psoriatic arthritis independent of the PSORS1 locus

Abstract

Objective. The strongest susceptibility locus of psoriatic arthritis (PsA) is within the major histocompatibility complex (MHC) region (psoriasis susceptibility region 1, or PSORS1), and HLA-Cw*06:02 has been reported as the PSORS1 susceptibility allele. Non-HLA genes within the MHC region have also been implicated in PsA, but because of the strong linkage disequilibrium at chromosome 6p21, it is difficult to make a distinction between susceptibility alleles and linked markers. Recent studies have demonstrated that the association between PsA and the tumor necrosis factor (TNF) promoter polymorphism TNF*-857 is independent of PSORS1. The aim of this study was to replicate the independent association of TNF*-857 in patients with PsA.Methods. A total of 909 patients with PsA and 1,315 healthy controls originating from the UK, Germany, and Italy were typed for TNF*-857 and for the estimated risk alleles of HLA-Cw*06:02.Results. Overall, the results of genotyping in these 3 case-control cohorts replicated the finding that the frequency of carriers of TNF*-857 TT/CT who were negative for the PSORS1 risk allele was significantly higher among patients with PsA compared with control subjects (30% versus 21%; P ‫؍‬ 9.17 ؋ 10 ؊5 ).Conclusion. The results of this collaborative study indicate that TNF*-857T is a susceptibility allele for PsA independent of the PSORS1 allele.

Correlations of TNF-α gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis in a northern Chinese Han population

“…A previous study has pointed out that the serum TNF-α level was increased in the -1031 T/C genotype carriers, and TNF-α polymorphism correlated with TNF-α level in patients with acute coronary syndrome. 32 Giardina et al 33 also demonstrated that TNF-α -857C/T might act as an independent risk factor for psoriatic arthritis, which is consistent with our study. Furthermore, from the study we observed that the patients with ocular MG showed lower frequencies of the TT genotype and the T allele of TNF-α -857C/ T than those with generalized MG. Ocular MG, prior to generalized MG stage, is an initial form of MG that accounts for~50% of all MG; although there has been a declined rate of ocular MG progressing to generalized MG in MG patients owing to the development of immuomodulation therapies including prednisone therapy, the disease progression is still inevitable.…”

TNF-αPolymorphisms in Juvenile Idiopathic Arthritis: Which Potential Clinical Implications?

“…Indeed the author suggests that this polymorphism is associated with higher TNF- α production [32]. Studies in adult patients have recently demonstrated that −857T allele is an independent risk allele for psoriatic arthritis [79, 80] but similar data were not founded in children. Zeggini et al examined the association of multiple TNF SNPs (−1031, −863, −857, −376, +489A, +851, +1304) with juvenile oligoarthritis by constructing and analyzing SNP-tagged TNF haplotype in 144 simplex families consisting of parents and affected children.…”

Pharmacogenomics of Multifactorial Diseases: A Focus on Psoriatic Arthritis

“…Concerning the environmental risk factors, it is important to mention: stress, low-humidity, drugs, smoking, obesity and chronic infections. In addition, numerous susceptibility genes and variants (LCE3B, LCE3C, TRAF3IP2, polymorphisms in IL-17, IL-23, RUNX3 and TNF*-857) have been recognized as contributing risk factors for PsA [15,[18][19][20][21][22][23][24]. Concerning the treatment of PsA, the available therapeutic approaches are mainly oriented to relief the inflammation and/or the associated-symptoms and to 'slow-down' the progression to more advanced and severe stages of the disease.…”