Advances in lupus genetics

Abstract

Purpose of review: The field of systemic lupus erythematosus (SLE) genetics has been advancing rapidly in recent years. This review will summarize recent advances in SLE genetics.

Recent findings: Genome-wide-association and follow-up studies have greatly expanded the list of associated polymorphisms, and much current work strives to integrate these polymorphisms into immune system biology and the pathogenic mediators involved in the disease. This review covers some current areas of interest, including genetic studies in non-European SLE patient populations, studies of pathogenic immune system subphenotypes such as type I interferon and autoantibodies, and a rapidly growing body of work investigating the functional consequences of the genetic polymorphisms associated with SLE.

Summary: These studies provide a fascinating window into human SLE disease biology. As the work proceeds from genetic association signal to altered human biology, we move closer to tailoring interventions based upon an individual's genetic substrate.

Figure 1

Schematic diagram illustrating potential pathways and causal chains linking genetic variations, functional genetic changes, immune system phenotypes, and physical phenotypes in SLE. Arrows are meant to indicate that one factor influences the other.

Figure 2

Summary of functional genetic changes discussed in the article, illustrating location relative to the gene structure. Transcriptional start site is indicated with the large black 90 degree arrow, gene exons are indicated by light blue rectangles, 3′ UTR region is a green rectangle, diagonal lines used to represent a large skipped interval, yellow outlined box indicates an enhancer element.