Association of Fcγ receptor IIB gene polymorphism with genetic susceptibility to systemic lupus erythematosus in Chinese populations—A family-based association study
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文摘

Summary

Background

The aim of this study was to investigate the role of FcγRIIB 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 FcγRIIB gene with respect to genetic susceptibility to SLE. The FcγRIIB gene was genotyped by restriction fragment length polymorphism (RFLP) method.

Results

Among 119 SLE patients, the frequencies of FcγRIIB-C50T CC, CT and TT genotypes were 12.7 % , 60.7 % and 26.6 % , respectively. The frequencies of FcγRIIB-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 FcγRIIB 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 (χ2 = 10.88, P = 0.0013; χ2 = 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 FcγRIIB-50T-225C haplotype might be the susceptible factor of SLE in Chinese population.

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