Association of tumor necrosis factor receptor 2 (TNFR2) polymorphism with susceptibility to systemic lupus erythematosus

Multiple genetic as well as environmental factors are considered to be invo lved in the development of systemic lupus erythematosus (SLE), A number of previous studies have suggested a possible role for tumor necrosis factor ( TNF) in the pathogenesis of SLE, In addition, one of the candidate loci sug gested by the genome-wide linkage analysis corresponds to the chromosomal p osition encompassing the TNF receptor 2 gene (TNFR2). The purpose of this s tudy was to analyze the polymorphism of TNFR2 and its possible association with the susceptibility to SLE, using the case-control association analysis . Polymorphism screening of the exons containing previously reported nonsyn onymous base substitutions was carried out by the polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) method, using genomic DNA from 81 Japanese patients with SLE and 207 healthy individuals. Two al leles were present in exon 6, coding for methionine (196M) and arginine (19 6R) at position 196. 30 of 81 patients (37.0%) with SLE were positive for t he 196R allele, which was significantly more frequent compared with 39 of 2 07 healthy individuals (18.8%) (chi(2) = 10.6, df = 1, P = 0.001, odds rati o = 2.53, 95% CI: 1.45-4.43), Genotype analysis revealed that the presence of one 196R allele was sufficient for rendering susceptibility. The associa tion of 196R allele with SLE was independent from that of HLA-DRB1*1501. In conclusion, the TNFR2 196R allele was found to he significantly associated with the susceptibility to SLE in the Japanese population, Further populat ion and functional studies will be of particular importance to establish TN FR2 as one of the susceptibility genes to SLE.