A novel single-nucleotide polymorphism of the Fcgamma receptor IIIa gene is associated with genetic susceptibility to systemic lupus erythematosus in Chinese populations: a family-based association study.

摘要

Background. Systemic lupus erytematosus (SLE) is characterized by the presence of various autoantibodies and the deposition of immune complexes which are cleared by Fcgamma receptors. Objectives. Family-based association analysis was performed to investigate whether the FCGR3A-72S/R and FCGR3A-270T/R polymorphisms are risk factors for SLE in a Chinese population. Methods. In total, 119 patients with SLE from 95 nuclear families, aged 14-78 years, who met the American College of Rheumatology 1997 criteria were recruited, as were 316 family members of these patients. We studied two single-nucleotide polymorphisms (SNPs) encoding nonsynonymous substitution in the FCGR3A gene with respect to genetic susceptibility to SLE in a collection of 435 subjects from 95 nuclear families. We performed the genotyping using PCR restriction fragment length polymorphism. Results. Our results showed that FCGR3A-72R/S have an excess of transmission of the R allele from heterozygous parents to affected offspring (transmission disequilibrium test chi(2) = 9.30, P = 0.0032). Univariate (single-marker) family-based association tests demonstrated that a variant allele at SNP rs403016 of the FCGR3A gene was significantly associated with genetic susceptibility to SLE (exon 3, Z = 2.5444, P = 0.01097) in an additive model. The R and S allele frequencies were 39.4% and 60.6%, respectively. The frequencies of FCGR3A 72R/R, R/S and SS genotypes were 9.1%, 60.6% and 30.3%, respectively. However, the FCGR3A-270T/S SNP was not found in this Chinese population. Conclusion. This study suggests a linkage disequilibrium of the FCGR3A-72R/S SNP with SLE, and supports the notion that a novel polymorphism of the FCGR3A-72R/S SNP is associated with genetic susceptibility to SLE in Chinese populations.