Fcγ Receptor IIIa Single‐Nucleotide Polymorphisms and Haplotypes Affect Human IgG Binding and Are Associated With Lupus Nephritis in African Americans. Issue 5 (May 2014)

• Record Type: Journal Article
• Authors: Dong, Chaoling; Ptacek, Travis S.; Redden, David T.; Zhang, Kui; Brown, Elizabeth E.; Edberg, Jeffrey C.; McGwin, Gerald; Alarcón, Graciela S.; Ramsey‐Goldman, Rosalind; Reveille, John D.; Vilá, Luis M.; Petri, Michelle; Qin, Aijian; Wu, Jianming; Kimberly, Robert P.
• Is Part Of: Arthritis & rheumatology. Volume 66:Issue 5(2014)
• Page Start: 1291
• Page End: 1299
• Publication Date: 2014-05
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.38337
• Languages: English
• ISSNs: 2326-5191

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art38337-sec-0001" sec-type="section"> <title>Objective</title> <p>To investigate whether the Fcγ receptor IIIa–66L/R/H (FcγRIIIa‐66L/R/H) polymorphism influences net effective receptor function and to assess if the <italic>FCGR3A</italic> combined genotypes formed by FcγRIIIa‐66L/R/H and FcγRIIIa‐176F/V, as well as copy number variation (CNV), confer risk of developing systemic lupus erythematosus (SLE) and lupus nephritis.</p> </sec> <sec id="art38337-sec-0002" sec-type="section"> <title>Methods</title> <p>FcγRIIIa variants, expressed on A20 IIA1.6 cells, were used in flow cytometry–based human IgG–binding assays. Using Pyrosequencing methodology, <italic>FCGR3A</italic> single‐nucleotide polymorphism and CNV genotypes were determined in a cohort of 1, 728 SLE patients and 2, 404 healthy controls.</p> </sec> <sec id="art38337-sec-0003" sec-type="section"> <title>Results</title> <p>The FcγRIIIa‐66L/R/H (rs10127939) polymorphism influenced ligand binding capacity in the presence of the FcγRIIIa‐176V (rs396991) allele. There was a trend toward an association of the low‐binding FcγRIIIa‐176F allele with lupus nephritis among African Americans (<italic>P</italic> = 0.0609) but not among European Americans (<italic>P</italic> > 0.10). Nephritis among African American patients with SLE was associated with FcγRIIIa low‐binding haplotypes containing the 66L/R/H and 176F variants (<italic>P</italic> = 0.03) and with low‐binding genotype combinations (<italic>P</italic> = 0.002). No association was observed among European American patients with SLE. The distribution of <italic>FCGR3A</italic> CNV was not significantly different among controls and SLE patients with or without nephritis.</p> </sec> <sec id="art38337-sec-0004" sec-type="section"> <title>Conclusion</title> <p>FcγRIIIa‐66L/R/H influences ligand binding. The low‐binding haplotypes formed by 66L/R/H and 176F confer enhanced risk of lupus nephritis in African Americans. <italic>FCGR3A</italic> CNVs are not associated with SLE or lupus nephritis in either African Americans or European Americans.</p> </sec> </abstract>