Genetic susceptibility and haplotype analysis between Fcγ receptor IIB and IIIA gene with systemic lupus erythematosus in Chinese population

Abstract

The objective of this study is to understand the role of FcγRIIB and FcγRIIIA gene in susceptibility to systemic lupus erythematosus (SLE), and to examine possible susceptible haplotypes between two genes. A total of 119 patients with SLE from 95 nuclear families, aged from 14 to 78 years, were selected according to 1997 criteria of American College of Rheumatology. In addition, 316 family members of these patients were also genotyped. A family-based association study was used to explore the relationship between gene polymorphism and SLE. We studied 13 single-nucleotide polymorphisms (SNPs) encoding non-synonymous substitution in the FcγRIIB and FcγRIIIA gene (four SNPs in the FcγRIIB gene and nine SNPs in the FcγRIIIA gene) with respect to genetic susceptibility to SLE. All SNPs were genotyped by restriction fragment length polymorphism method. Among 13 SNPs, univariate (single-marker) family-based association tests showed that variant alleles at only four SNPs (rs10917661 and rs1050501, in exon 2 and exon 5 of FcγRIIB gene, rs403016 and rs428888, in exon3 of FcγRIIIA gene respectively) were significantly associated with genetic susceptibility to SLE. Furthermore, the haplotype-specific FBATs showed 50Ter-225Thr (34.1%, in FcγRIIB gene) and 72Arg-118Asn (40%, in the FcγRIIIA gene) haplotype were more frequently transmitted in SLE than other haplotypes (Z = 3.539, P = 0.00042; Z = 2.678, P = 0.007412 respectively). But haplotypes were not found between FcγRIIB and FcγRIIIA gene Our results suggest that there were meaningful haplotype in FcγRIIIA and FcγRIIB gene respectively. FcγRIIIA and FcγRIIB genes in the pathogenesis of SLE may play an independent role in Chinese population.

Keywords

Chinese family based association test FcγRIIB FcγRIIIA haplotype lupus erythematosus polymorphism single nucleotide systemic susceptibility

Get full access to this article

View all access options for this article.

References

1 Salmon JE Pricop L . Human receptors for immunoglobulin G. Arthritis Rheum 2001; 44: 739 – 750 .

2 Qin D Wu J Vora KA . Fcγ receptor IIB on follicular dendritic cells regulates the B cell recall response. J Immunol 2000; 164: 6268 – 6275 .

3 Tew JG Wu J Fakher M Szakal AK Qin D . Follicular dendritic cells:beyond the necessity of T-cell help. Trends Immunol 2001; 22: 361 – 367 .

4 Haberman AM Shlomchik MJ . Reassessing the function of immune-complex retention by follicular dendritic cells. Nat Rev Immunol 2003; 3: 757 – 764 .

5 Kosco-Vilbois MH . Are follicular dendritic cells really good for nothing? Nat Rev Immunol 2003; 3: 764 – 769 .

6 Takai T Ono M Hikida M Ohmori H Ravetch JV . Augmented humoral and anaphylactic responses in Fc gamma RII-dificient mice. Nature 1996; 379: 346 – 349 .

7 Clynes R Maizes JS Guinamard R Ono M Takai T Ravetch JV . Modulation of immune complex-induced inflammation in vivo by the coordinate expression of activation and inhibitory Fcγ receptors. J Exp Med 1999; 89: 179 – 185 .

8 Hatta Y Tsuchiya N Ohashi J . Association of Fcγ receptor IIIB, but not of Fcγ receptor IIa and IIIa, polymorphisms with systemic lupus erythematosus in Japanese. Genes Immun 1999; 1: 53 – 60 .

9 Kyogoku C Tsuchiya N Matsuta K Tokunaga K . Studies on the association of Fcγ receptor IIa, IIb, IIIa and IIIb polymorphisms with systemic lupus rheumatoid arthritis in the Japanese: evidence for a genetic interaction between HLA-DRB1 and FcγRIIIA. Genes Immun 2002; 3: 488 – 493 .

10.

11.

12.

12 Rabinowitz D Laird N . A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information. Hum Hered 2000; 50: 211 – 223 .

13.

13 Horvath S Xu X Lake SL Silverman EK Weiss ST Laird NM . Family-based tests for associating haplotypes with general phenotype data, Application to asthma genetics. Genet Epidemiol 2004; 26: 61 – 69 .

14.

14 Excoffier L Slatkin M . Maximum-likelihood estimation of molecular haplotypes frequencies in a diploid population. Mol Biol Evol 1995; 12: 921 – 927 .

15.

15 Ravetch JV Bolland S . IgG Fcγ receptors. Ann Rev Immunol 2001; 19: 275 – 290 .

16.

16 Bolland S Ravetch JV . Spontaneous autoimmune disease in FcγRIIB-deficient mice results from strain-specific epistasis. Immunity 2000; 13: 277 – 285 .

17.

17 Jiang Y Hirose S Abe M . Polymorphisms in IgG Fcγ receptor IIB regulatory regions association with autoimmune susceptibility. Immunogenetics 2000; 51: 429 – 435 .

18.

18 Slingsby JH Hogarth MB Walport MJ Morley BJ . Polymorphism in the Ly-17 alloantigenic system of the mouse FcγRII gene. Immunogenetics 1997; 46: 361 – 362 .

19.

19 Amoura Z Koutouzov S Chabre H . Presence of antinucleosome autoantibodies in a restricted set of connective tissue diseases. Antinucleosome antibodies of the IgG3 subclass are markers of renal pathogenicity in systemic lupus erythematosus. Arthritis Rheum 2000; 43: 76 – 84 .

20.

20 Selvaraj P Rosse WF Silber R Springer TA . The major Fcγ receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal nocturnal haemoglobinuria. Nature 1988; 333: 565 – 567 .

21.

21 Kyogoku C Dijstelbloem HM Tsuchiya N . Fcγ receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FcγRIIB to genetic susceptibility. Arthritis Rheum 2002; 46: 1242 – 1254 .