Rheumatology Advance Access published online on February 28, 2003
Rheumatology, doi:10.1093/rheumatology/keg157
Rheumatology © British Society for Rheumatology 2003; all rights reserved
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Original Papers
1 University of Pennsylvania School of Medicine, Philadelphia
* Corresponding author. E-mail: sullivak{at}mail.med.upenn.edu.
Received 23 May 2003
; accepted 9 October 2002
Objectives. Systemic lupus erythematosus (SLE) is a polygenic disorder of dysregulated inflammation. Numerous specific candidate genes have been identified and most relate to the handling of immune complexes or antigen presentation. This is consistent with the classic finding of immune complex deposition in affected end organs. We wished to examine combinatorial effects of polymorphic variants of genes involved in immune complex clearance in susceptibility to lupus. Methods. This study examined the occurrence of polymorphisms in genes which encode proteins known to be involved in immune complex handling and clearance. Each polymorphic variant of a complement protein (C2, mannose binding protein and C4), complement receptor (CR1) or Fc receptor (Fc Results. We found an increasing association of SLE with increasing numbers of gene defects. Combinations of severe defects in Fc Conclusions. The results of the study suggest that genes may interact in ways that either synergize or modify the effect of a single genetic effect and imply that association studies must be interpreted within the genetic background of the populations.
Analysis of polymorphisms affecting immune complex handling in systemic lupus erythematosus
2 Children's Hospital of Philadelphia, Philadelphia, PA
3 Johns Hopkins University School of Medicine, Baltimore, MD, USA
RIIA and FcRIIIA) gene is known to affect function adversely. One hundred and sixty SLE patients and 212 control subjects were genotyped using polymerase chain reaction methods.RIIA and FcRIIIA were particularly deleterious for both African American and Caucasian patients, even though only one defective variant was individually statistically significantly associated with SLE.
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