FCGR3B copy number variation is not associated with lupus nephritis in a Chinese population

Abstract

Copy number variation (CNV) is common in genomic regions encoding immune-related genes and can impact polygenic autoimmunity. FCGR3B CNV is associated with susceptibility to systemic autoimmunity in Caucasian populations. In this study, we examined FCGR3B CNV in patients with the autoimmune disease lupus nephritis (LN) in a Chinese population. The study includes 202 patients with histologically verified LN and 146 geographically matched healthy controls. To identify CNV at the FCGRB locus, quantitative polymerase chain reaction (PCR) was done with TaqMan^TM probes and relative copy number was estimated with relative quantitative 2^—ΔΔCt method. The distribution of FCGR3B relative copy number did not differ significantly between the LN patients and the controls (1.17 ± 0.42 for LN; 1.15 ± 0.37 for controls; p = 0.627). The difference was still not significant when the data were stratified by gender. There was no significant difference when the LN patients were divided by pathological phenotype (proliferative LN compared with non-proliferative p = 0.511; AI < 12 compared with AI ≥ 12, p = 0.401; and chronicity index (CI) < 4 compared with CI ≥ 4, p = 0.058) or lupus disease activity index (SLEDAI ≤ 10 compared with SLEDAI > 10, p = 0.996). The data suggest that FCGR3B CNV was not associated with LN development or progression in this Chinese population. These results were surprising given the strong in a Caucasian population. Lupus (2010) 19, 158—161.

Keywords

copy number variance FCGR3B genetics lupus nephritis

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References

Redon R. , Ishikawa S. , Fitch KR , et al. Global variation in copy number in the human genome. Nature 2006; 444: 444-454.

Gonzalez E. , Kulkarni H. , Bolivar H. , et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 2005 ; 307: 1434-1440.

Hollox EJ , Huffmeier U. , Zeeuwen PL , et al. Psoriasis is associated with increased beta-defensin genomic copy number. Nat Genet 2008; 40(1): 23-25.

Yang, Y. , Chung EK , Wu YL , et al. Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans. Am J Hum Genet 2007; 80: 1037-1054.

Aitman TJ , Dong R. , Vyse TJ , et al. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature 2006; 439: 851-855.

Takai T. Roles of Fc receptors in autoimmunity. Nat Rev Immunol 2002; 2(8): 580-592.

Nimmerjahn F. , Ravetch JV Fcgamma receptors as regulators of immune responses. Nat Rev Immunol 2008; 8(1): 34-47.

Fanciulli M. , Norsworthy PJ , Petretto E. , et al. FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific autoimmunity. Nat Genet 2007; 39(6): 721-723.

Willcocks LC , Lyons PA , Clatworthy MR , et al. Copy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake. J Exp Med 2008; 205(7): 1573-1582.

10.

Schwarting A.

Genetic predisposition-is lupus nephritis a question of copy numbers?

Nephrol Dial Transplant 2006; 21(9): 2378-2379.

11.

Patel M. , Clarke AM , Bruce IN , Symmons DP The prevalence and incidence of biopsy-proven lupus nephritis in the UK: evidence of an ethnic gradient. Arthritis Rheum 2006 ; 54(9): 2963-2969.

12.

Hebbring SJ , Adjei AA , Baer JL , et al. Human SULT1A1 gene: copy number differences and functional implications. Hum Molec Genet 2007; 16(5): 463-470.

13.

Szilagyi A. , Blasko B. , Szilassy D. , Fust G. , Sasvari-Szekely M. , Ronai Z. Real-time PCR quantification of human complement C4A and C4B genes. BMC Genet 2006; 10(7): 1-9.

14.

Kelley J. , Johnson MR , Alarcón GS , Kimberly RP , Edberg JC Variation in the relative copy number of the TLR7 gene in patients with systemic lupus erythematosus and healthy control subjects. Arthritis Rheum 2007; 56(10): 3375-3378.

15.

Chen Q. , Book M. , Fang X. , Hoeft A. , Stuber F. Screening of copy number polymorphisms in human β-defensin genes using modified real-time quantitative PCR. J Immunol Methods 2006; 308(1-2): 231-240.

16.

De Preter K. , Speleman F. , Combaret V. , et al. Quantification of MYCN, DDX1, and NAG gene copy number in neuroblastoma using a real-time quantitative PCR assay . Mol Pathol 2002; 15(2): 159-166.

17.

Mitrecić D. , Huzak M. , Curlin M. , Gajović S. An improved method for determination of gene copy numbers in transgenic mice by serial dilution curves obtained by real-time quantitative PCR assay. J Biochem Biophys Methods 2005; 64(2): 83-98.

18.

Hoebeeck J. , Speleman F. , Vandesompele J. Real-time quantitative PCR as an alternative to Southern blot or fluorescence in situ hybridization for detection of gene copy number changes. Methods Mol Biol 2007 ; 353: 205-226.

19.

Chu ZT , Tsuchiya N. , Kyogoku C. , et al. Association of Fc gamma receptor IIb polymorphism with susceptibility to systemic lupus erythematosus in Chinese: a common susceptibility gene in the Asian populations. Tissue Antigens 2004 ; 63: 21-27.

20.

Chen JY , Wang CM , Ma CC , et al. Association of a transmembrane polymorphism of Fcgamma receptor IIb (FCGR2B) with systemic lupus erythematosus in Taiwanese patients. Arthritis Rheum 2006; 54: 3908-3917.

21.

Pan F. , Zhang K. , Li X. , Xu J. , Hao J. , Ye D. Association of Fcgamma receptor IIB gene polymorphism with genetic susceptibility to systemic lupus erythematosus in Chinese populations-a family-based association study. J Dermatol Sci 2006; 43: 35-41.

22.

Pan F. , Ye D. , Zhang K. , Li X. , Xu J. , Chen H. Gln50Ter Polymorphism of Fc gamma receptor IIB gene associated with genetic susceptibility to human systemic lupus erythematosus in Chinese populations . Arch Dermatol Res 2007; 299: 47-51.

23.

Kyogoku C. , Dijstelbloem HM , Tsuchiya N. , et al. Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility . Arthritis Rheum 2002; 46: 1242-1254.

24.

Siriboonrit U. , Tsuchiya N. , Sirikong M. , et al. Association of Fc gamma receptor IIb and IIIb polymorphisms with susceptibility to systemic lupus erythematosus in Thais. Tissue Antigens 2003; 61: 374-383.

25.

Kyogoku C. , Tsuchiya N. , Wu H. , Tsao BP , Tokunaga K. Association of Fc gamma receptor IIA, but not IIB and IIIA, polymorphisms with systemic lupus erythematosus: a family-based association study in Caucasians . Arthritis Rheum 2004; 50: 671-673.

26.

Magnusson V. , Johanneson B. , Lima G. , Odeberg J. , Alarcon-Segovia D. , Alarcon-Riquelme ME Both risk alleles for FcgammaRIIA and FcgammaRIIIA are susceptibility factors for SLE: a unifying hypothesis. Genes Immun 2004 ; 5: 130-137.

27.

Li X. , Wu J. , Carter RH , et al. A novel polymorphism in the Fcgamma receptor IIB (CD32B) transmembrane region alters receptor signaling. Arthritis Rheum 2003; 48: 3242-3252.

28.

Magnusson V. , Zunec R. , Odeberg J. , et al. Polymorphisms of the Fcgamma receptor type IIB gene are not associated with systemic lupus erythematosus in the Swedish population. Arthritis Rheum 2004; 50: 1348-1350.