Extensive genetic polymorphism in the haplotype STR-TNF and HLA class I with the onset and evolution of psoriasis vulgaris

Psoriasis is an inflammatory and autoimmune disease, clinically characterized by hyperproliferation of epidermis. The cause of the disease is unknown, but one of its most consistent associations involves the Major Histocompatibility Complex (MHC) and triggering factors [ ]. Many genes are located in the MHC region and the most important is the tumor necrosis factor-alpha (TNF-α). Several polymorphisms, including microsatellites (Short Tandem Repeats – STR), were identified in the TNF-α gene found in the MHC class III region. Some studies point out that those polymorphisms are related to the production level of the TNF-α cytokine and that they play an important role in inflammatory response [ ]. In the present study, Brazilian patients with psoriasis were divided according to onset of disease and the possible association of haplotypes formed by markers HLA class I genes and STR-TNF was examined. We further evaluated their role in relation to the favorable or unfavorable evolution of the disease. Typing of HLA class I and TNF (a–e) STRs was carried out in 60 patients, between 18 and 80 years of age, assisted at the outpatient dermatology clinic of the Teaching Hospital, University of Campinas, who were diagnosed according to defined clinical criteria. Diagnoses and follow-up were performed by experienced dermatologists. Based on criteria described by Henseler and Christophers for psoriasis vulgaris of early and late onset, 38 patients had type I psoriasis (PsVI) – onset before the age of 40 – and 22 patients had type II psoriasis (PsVII) – onset after the age of 40 [ ]. Patients were chosen at random regarding onset of the disease. The control group consisted of 60 genetically unrelated individuals between 18 and 53 years of age who were genetically unrelated and did not show clinical psoriasis lesion and/or family history of the disease, as well as voluntaries of the Hemotherapy service of the University of Campinas. Blood samples were obtained from both psoriasis patients and controls. DNA was isolated by a salting out procedure [ ] and HLA-B and -C alleles were identified by sequence specific primers (PCR/SSP) [ ]. The TNFa, b, c, d, and e microsatellite alleles were amplified by PCR using primers described by Udalova et al. [ ] and visualized in denaturizing polyacrylamide gels, in specific electrophoretic conditions.