The study that demonstrated that the major histocompatibility complex (MHC) region contains the strongest, most replicable susceptibility region for psoriasis and psoriatic arthritis was one of the first to implicate genetics in the development of psoriasis (https://ard.bmj.com/content/70/4/690.abstract). A new study from the University of Rome provides new evidence for the genetic link to psoriasis, where researchers have confirmed that TNF*-857T, a promoter polymorphism, is a susceptibility allele for psoriatic arthritis.
Under the direction of lead researcher Emiliano Giardina, PhD, of the University of Rome, the researchers assessed allele and genotype frequencies of TNF*-857 in three cohorts of Europeans from Germany (374 cases and 561 controls), Italy (400 cases and 400 controls) and Great Britain (135 cases and 354 controls). Overall, the allele frequency of TNF*-857T was significantly higher individuals with psoriatic arthritis (27%) than individuals without the disease (20%).
“In this collaborative work, we replicated the association of TNF*-857T as a susceptibility allele for [psoriatic arthritis] independent of the main PSORS1 risk allele,” Dr. Giardina said.
The researchers calculated the genotype frequencies of individuals who were positive and negative for the PSORS1 risk allele in an effort to verify an association regardless of the PSORS1 risk allele.
“Overall, the frequency of heterozygous or homozygous carriers of TNF*-857T (TT/CT) in individuals negative for the PSORS1/HLA-C risk allele was significantly higher in [psoriatic arthritis] patients (30%) than in control patients (21%),” the authors wrote in Arthritis and Rheumatism, yielding an odds ratio of 1.27. “As expected, the haplotype analysis confirmed TNF*-857T as a susceptibility factor independent of the PSORS1/HLA-C risk allele.”
The researchers report that the functional role of TNF*-857T has yet to be determined, but previous data shows that the allele may increase the transcription of TNF-alpha, which is known to play a significant role in both the activation and extravasation of T-cells in the highly vascularized synovium and in subchondral osteoclastogenesis promoting bone erosions. This link could mean that genes that encode for TNF-alpha are candidates for therapeutic markers.
