Springer Seminars in Immunopathology

, Volume 28, Issue 2, pp 119–130

Unraveling the genetics of systemic lupus erythematosus

  • John B. Harley
  • Jennifer A. Kelly
  • Kenneth M. Kaufman
Review

DOI: 10.1007/s00281-006-0040-5

Cite this article as:
Harley, J.B., Kelly, J.A. & Kaufman, K.M. Springer Semin Immun (2006) 28: 119. doi:10.1007/s00281-006-0040-5

Abstract

The capacity to locate polymorphisms on a virtually complete map of the human genome coupled with the ability to accurately evaluate large numbers (by historical standards) of genetic markers has led to gene identification in complex diseases, such as systemic lupus erythematosus (SLE or lupus). While this is a phenotype with enormous clinical variation, the twin studies and the observed familial aggregation, along with the genetic effects now known, suggest a strong genetic component. Unlike type 1 diabetes, lupus genetics is not dominated by the powerful effect of a single locus. Instead, there are at least six known genetic association effects in lupus of smaller magnitude (odds ratio <2), and at least 17 robust linkages (established and arguably confirmed independently) defining potentially responsible genes that largely remain to be discovered. The more convincing genetic associations include the human leukocyte antigen region (with multiple genes), C1q, PTPN22, PDCD1, Fc receptor-like 3, FcγRIIA, FcγRIIIA, interferon regulatory factor 5, and others. How they contribute to disease risk remains yet to be clarified, beyond the obvious speculation derived from what has previously been learned about these genes. Certainly, they are expected to contribute to lupus risk independently and in combination with each other, with genes not yet identified, and with the environment. A substantial number of genes (>10) are expected to be identified to contribute to lupus or in its many subsets defined by clinical and laboratory features.

Keywords

SLE Lupus Genetics Gene Polymorphism 

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • John B. Harley
    • 1
    • 2
    • 3
  • Jennifer A. Kelly
    • 2
  • Kenneth M. Kaufman
    • 1
    • 2
    • 3
  1. 1.Department of MedicineUniversity of OklahomaOklahoma CityUSA
  2. 2.Oklahoma Medical Research FoundationOklahoma CityUSA
  3. 3.US Department of Veterans Affairs Medical CenterOklahoma CityUSA

Personalised recommendations