ASSOCIATION OF TUMOR NECROSIS FACTOR RECEPTOR 2 (TNFR2) POLYMORPHISM WITH SUSCEPTIBILITY TO SYSTEMIC LUPUS ERYTHEMATOSUS

ASSOCIATION OF TUMOR NECROSIS FACTOR RECEPTOR 2 (TNFR2) POLYMORPHISM WITH SUSCEPTIBILITY TO SYSTEMIC LUPUS ERYTHEMATOSUS.
T Komata, N Tsuchiya, M Matsushita, K Hagiwara and K Tokunaga, Department of Human Genetics and Department of Allergy and Rheumatology, University of Tokyo, Tokyo, Japan.

Multiple genetic as well as environmental factors are considered to be involved in the development of rheumatic diseases. A number of previous studies suggested a possible role for tumor necrosis factor (TNF) in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, in both diseases, 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 these disorders, using the case-control association analysis. Variation screening of the coding regions was carried out by PCR-single strand conformation polymorphism (SSCP) method, using genomic DNA from Japanese patients and 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 196R allele, which was significantly more frequent compared with 39 of 207 healthy individuals (18.8%) (chi-square value =10.6, df=1, P=0.001, odds ratio = 2.53, 95% confidence interval : 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. No significant difference in the genotypes was observed between patients with RA and healthy individuals. Although several other single nucleotide polymorphisms (SNPs) were detected, significant association with the disease was observed only in 196M/R polymorphism. In conclusion, TNFR2 196R allele was found to be significantly associated with the susceptibility to SLE in the Japanese population.