Multiple genetic as well as environmental factors are considered to be involved 
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 suggested by the 
genome-wide linkage analysis corresponds to the chromosomal position 
encompassing the TNF receptor 2 gene (TNFR2). The purpose of this study 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 nonsynonymous 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 alleles were present 
in exon 6, coding for methionine (196M) and arginine (196R) at position 196. 30 
of 81 patients (37.0%) with SLE were positive for the 196R allele, which was 
significantly more frequent compared with 39 of 207 healthy individuals (18.8%) 
(chi2=10.6, df=l, P=0.001, odds ratio=2.53, 95% CI: 1.45-4.43). Genotype 
analysis revealed that the presence of one 196R allele was sufficient for 
rendering susceptibility. The association of 196R allele with SLE was 
independent from that of HLA-DRB1*1501. In conclusion, the TNFR2 196R allele was 
found to be significantly associated with the susceptibility to SLE in the 
Japanese population. Further population and functional studies will be of 
particular importance to establish TNFR2 as one of the susceptibility genes to 
SLE.