Background: The aim of this study was to investigate the role of FcgammaRIIB gene in susceptibility to systemic lupus erythematosus (SLE) using family-based association analysis method, and to examine possible haplotypes between two single-nucleotide polymorphisms.
Objective: A total of 119 patients with SLE from 95 nuclear families, aged from 14 to 78 years, was selected according to 1997 criteria of American College of Rheumatology (ACR), In addition, 316 family members of these patients were also genotyped.
Methods: A family-based association study was used to explore the relationship between gene polymorphism and SLE. We studied two single-nucleotide polymorphisms (SNPs) encoding non-synonymous substitution in the FcgammaRIIB gene with respect to genetic susceptibility to SLE. The FcgammaRIIB gene was genotyped by restriction fragment length polymorphism (RFLP) method.
Results: Among 119 SLE patients, the frequencies of FcgammaRIIB-C50T CC, CT and TT genotypes were 12.7%, 60.7% and 26.6%, respectively. The frequencies of FcgammaRIIB-T225C TT, TC and CC genotypes were 8.1%, 61.3% and 30.6%, respectively. Four haplotypes, 50T-225C (34.1%), 50C-225C (27.7%), 50T-225T (19.7%) and 50C-50T (18.5%) were reconstructed. Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at two SNPs, rs10917661 and rs1050501, in exons 2 and 5 of FcgammaRIIB gene were significantly associated with genetic susceptibility to SLE in additive model (exon 2, Z=3.444, P=0.00057; exon 5, Z=3.707, P=0.00020), respectively. Transmission/disequilibrium test (TDT) and sibship disequilibuium test (SDT) analysis showed an excess of the alleles of T (C50T) and C (T225/C) from heterozygous parents to affected offspring (chi(2)=10.88, P=0.0013; chi(2)=7.14, P=0.0105, respectively). Furthermore, the haplotype-specific FBATs showed 50T-225C (34.1%) haplotype was more frequently transmitted in SLE than other haplotypes (Z=3.539, P=0.00042).
Conclusions: Our findings provide strong evidence suggesting the FcgammaRIIB-50T-225C haplotype might be the susceptible factor of SLE in Chinese population.