Role of Fcγ receptor IIb polymorphism in the genetic background of systemic lupus erythematosus: Insights from Asia

Abstract

FCGR2B codes for an inhibitory receptor expressed in B cells and monocytes. Polymorphisms of Fcgr2b in mice have been shown to be associated with autoimmune diseases including systemic lupus erythematosus (SLE) and targeted disruption of Fcgr2b renders mice susceptible to induced or spontaneous autoimmunity, depending on the genetic background. Polymorphism screening of FCGR2B has been hampered by the complexity and extreme homology among FCGR family members. We established a specific genotyping system, detected a SNP that changes position 232 amino acid in the transmembrane region from Ile to Thr and found a significant association of 232Thr with SLE in the Japanese, Thai and Chinese populations. In contrast, promoter polymorphism of FCGR2B, but not Ile232Thr, was shown to be associated with SLE in Caucasians. Linkage disequilibrium was observed among FCGR2A, 2B, 3A and 3B genes with varying degrees, but in the Asian populations, each of FCGR2B, 3A and 3B genes was suggested to contribute to the susceptibility to SLE. These results indicate that FCGR2B is a susceptibility gene to SLE in the context of a genetic background, both in humans and mice.

• Systemic lupus erythematosus
• transmembrane region
• amino acid
• environmental factors

Acknowledgements

In accordance with the purpose of this issue of the journal, we would like to acknowledge a number of Japanese investigators who made tremendous contributions in the research of this inhibitory, but nonetheless fascinating, molecule. We are grateful to a large number of investigators and graduate students in five countries involved in the FcγRIIb project for such a fruitful collaboration. This work was supported by Grant-in-Aid for Scientific Research on Priority Areas (C) “Medical Genome Science”, Grant-in-Aid for Scientific Research (B) from the Ministry of Education, Science, Sports and Culture of Japan, and by Health and Labour Sciences Research Grant from the Ministry of Health Labour and Welfare of Japan.