Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans

Salmon, Jane E., Millard, Sean, Schachter, Leah A., Arnett, Frank C., Ginzler, Ellen M., Gourley, Mark F., Ramsey-Goldman, Rosalind, Peterson, Margaret G.E. and Kimberly, Robert P. (1996) Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans. Journal of Clinical Investigation, 97 5: 1348-1354. doi:10.1172/JCI118552

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Author Salmon, Jane E.
Millard, Sean
Schachter, Leah A.
Arnett, Frank C.
Ginzler, Ellen M.
Gourley, Mark F.
Ramsey-Goldman, Rosalind
Peterson, Margaret G.E.
Kimberly, Robert P.
Title Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans
Formatted title
FcγRIIA alleles are Heritable risk factors for lupus nephritis in African Americans
Journal name Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0021-9738
Publication date 1996-03-01
Sub-type Article (original research)
DOI 10.1172/JCI118552
Open Access Status File (Publisher version)
Volume 97
Issue 5
Start page 1348
End page 1354
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Abstract Allelic variants of Fc gamma R confer distinct phagocytic capacities providing a mechanism for heritable susceptibility to immune complex disease. Human Fc gamma RIIa has two codominantly expressed alleles, R131 and H131, which differ substantially in their ability to ligate human IgG2. The Fc gamma RIIa-H131 is the only human Fc gamma R which recognizes IgG2 efficiently and optimal IgG2 handling occurs only in the homozygous state. Therefore, since immune complex clearance is essential in SLE, we hypothesized that Fc gamma RIIA genes are important disease susceptibility factors for SLE, particularly lupus nephritis. In a two-stage cross-sectional study, we compared the distribution of Fc gamma RIIA alleles in African Americans with SLE to that in African American non-SLE controls. A pilot study of 43 SLE patients and 39 controls demonstrated a skewed distribution of Fc gamma RIIA alleles, with only 9% of SLE patients homozygous for Fc gamma RIIa-H131 compared with 36% of controls (odds ratio, 0.18; 95% CI, 0.05-0.69, P = 0.009). This was confirmed with a multicenter study of 214 SLE patients and 100 non-SLE controls. The altered distribution of Fc gamma RIIA alleles was most striking in lupus nephritis. Trend analysis of the genotype distribution showed a highly significant decrease in Fc gamma RIIA-H131 as the likelihood for lupus nephritis increased (P = 0.0004) consistent with a protective effect of the Fc gamma RIIA-H131 gene. The skewing in the distribution of Fc gamma RIIA alleles identifies this gene as a risk factor with pathophysiologic importance for the SLE diathesis in African Americans.
Keyword Fc gamma receptors
Systemic lupus erythematosus
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
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Created: Fri, 04 Mar 2016, 11:34:46 EST by Ms Joanne Biles on behalf of School of Biomedical Sciences