Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility.

摘要: Objective Human low-affinity Fcγ receptors (FcγR) constitute a clustered gene family located on chromosome 1q23, that consists of FcγRIIA, IIB, IIC, IIIA, and IIIB genes. FcγRIIB is unique in its ability to transmit inhibitory signals, recent animal studies demonstrated role for deficiency the development autoimmunity. Genetic variants their association with systemic lupus erythematosus (SLE) have been extensively studied various populations, but results were inconsistent. To examine possibility another susceptibility primary significance exists within FcγR region, we screened polymorphisms human FCGR2B gene, examined whether these are associated SLE. Methods Variation screening was performed by direct sequencing polymerase chain reaction (PCR)-single-strand conformation polymorphism methods using complementary DNA samples. Genotyping detected done genomic DNA, specific genotyping system based nested PCR hybridization probing. Association SLE analyzed 193 Japanese patients 303 healthy individuals. In addition, same groups controls genotyped previously known FCGR2A, FCGR3A, FCGR3B. Results We single-nucleotide FCGR2B, (c.695T>C), coding nonsynonymous substitution, Ile232Thr (I232T), transmembrane domain. The frequency 232T/T genotype significantly increased compared When also FCGR2A-131R/H, FCGR3A-176V/F, FCGR3B-NA1/2 polymorphisms, FCGR3A-176F/F showed significant association. Two-locus analyses suggested both FCGR3A may contribute susceptibility, while reported FCGR3B considered be secondary derived from strong linkage disequilibrium FCGR2B. Conclusion These demonstrate new (I232T) Japanese.