Genetic linkage and association of Fcγ receptor IIIA (CD16A) on chromosome 1q23 with human systemic lupus erythematosus

Abstract

Objective. Although low-affinity alleles of human Fc␥ receptor types IIA and IIIA (Fc␥RIIA and Fc␥RIIIA, respectively) polymorphisms have been associated with systemic lupus erythematosus (SLE) in case-control studies, the relative contribution of these genes to SLE susceptibility has not been resolved.Methods. We analyzed the distribution of alleles of Fc␥RIIA, Fc␥RIIIA, and Fc␥RIIIB in 126 multiplex-SLE pedigrees and Fc␥RIIA and Fc␥RIIIA in a casecontrol replication study, using allele-specific polymerase chain reaction and direct sequencing of genomic DNA. Statistical tests of association were performed to detect evidence of linkage between the single nucleotide polymorphisms and SLE. Conclusion. To our knowledge, these data are the first to demonstrate linkage and both family-based and case-control-based association of Fc␥RIIIA with SLE. These data provide genetic evidence supporting a role for the physiologically relevant single nucleotide polymorphism of the Fc␥RIIIA gene in the pathophysiology of this complex genetic disease.Systemic lupus erythematosus (SLE) (MIM no. 152700; see the Online Mendelian Inheritance in Man Web site at http://www.ncbi.nlm.nih.gov/omim) is a systemic autoimmune disease characterized by the production of autoantibodies directed against nuclear antigens

Association of Fcγ receptor IIA, but not IIB and IIIA, polymorphisms with systemic lupus erythematosus: A family‐based association study in Caucasians

“…In fact, no infiltration of activated lymphocytes is observed in the arthritic joints of animals with CAIA (11). In contrast, CIA is a well-known model of chronic arthritis that is dependent on both humoral and cellular immunity specific for CII, and is especially dependent on Th1 activation (4,10). In this study, there were no notable differences in the serum levels of anti-CII IgG antibodies (total IgG and subclasses IgG1 and IgG2a) between the 2 groups of mice, which suggests that the Th1/Th2 balance in CIA is not changed by OPN deletion.…”

“…The serum levels of total IgG and of specific antibodies to CII (total IgG and subclasses IgG1 and IgG2a) were measured by ELISA as previously described (10), with minor modifications. Ninetysix-well plates were coated with anti-mouse IgG (Caltag, Burlingame, CA) or bovine CII antigen solution (2 g/ml).…”

Biomarkers in systemic lupus erythematosus: I. General overview of biomarkers and their applicability

“…A linkage between SLE and the F176 allele (alternative designation of F158) of Fc␥RIIIa was demonstrated using both family-based and case-control methods (42). Family-based tests of association (transmission disequilibrium test and pedigree disequilibrium test) demonstrated increased transmission of the F176 allele (OR 2.18, P Ͻ 0.002) in families of both African American and European American ancestry.…”

Genomic organization of classical human low-affinity Fcγ receptor genes

“…[7][8][9][10][11] Polymorphisms in the ligand binding sites of both Fc␥RIIA and Fc␥RIIIA, which alter ligand binding and receptor function, are associated with SLE, 12-18 and we have recently described both linkage and association of Fc␥RIIIA locus with SLE in casecontrol and family-based studies. 19 Additional variations in the human Fc␥Rs, such as the stop codon polymorphism in Fc␥RIIC extracellular domain 1, [20][21][22][23] might also play a role in SLE. However, analysis has been hampered by the very high homology among several of these genes, which is most likely the result of duplication and recombination in the evolution of this cluster.…”