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

Systemic lupus erytematosus (SLE) is characterized by the presence of various autoantibodies and the deposition of immune complexes which are cleared by Fc gamma receptors. 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. 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. 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. 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.