Genetic Variant Linked to Lupus

Systemic lupus erythematosus (SLE or lupus), a prototypic autoimmune disease, is characterized by system-wide chronic inflammation. Scientists’ best information indicates that it is caused by a complex interaction of multiple genes on different chromosomes and unknown environmental factors.

What Problem Was Studied?
Studies have shown that type I interferon plays a role in the development and progression of lupus. Genes that regulate the interferon system have likewise been shown to be related to lupus activity and severity. Interferon regulatory factor 5 (IRF5) is a transcription factor that regulates type I interferon production as well as the induction of the proinflammatory cytokines interleukin-6, interleukin-12 and tumor necrosis factor-a.

A team of scientists from the University of Pittsburgh and Northwestern University in Chicago sought to replicate results of previous studies linking a variant of IRF5 and lupus. Included among this research team are two past recipients of Arthritis Foundation clinical sciences grants: Susan Manzi, MD, MPH, of University of Pittsburgh and Rosalind Ramsey-Goldman, MD, MPH, of Northwestern University.

What Was Done in the Study?
DNA samples were taken from the blood of 370 white women with lupus and 462 white women without lupus. The samples were genotyped for the IRF5 variant called rs2004640. The frequency of the allele in question was calculated and compared between the two groups.

What Were the Study Results?
The genotyping showed significant differences between women with lupus and women without lupus. Through specialized statistical calculations, the team was able to confirm that there is “a genuine association with a modest effect” between the IRF5 variant rs2004640 and the risk of developing lupus.

What Does This Mean For People With Lupus?
Senior investigator M. Ilyas Kamboh, PhD, summarized the importance of the study results in the article’s conclusion. “Understanding the molecular mechanisms pertaining to IRF5 function and the spectrum of IRF5-targeted genes will increase our knowledge about SLE etiopathogenesis and may guide novel therapeutic strategies for SLE and other autoimmune diseases.”

Demirci FYK, Manzi S, Ramsey-Goldman R, et al. Association of a common interferon regulatory factor 5 (ERF5) variant with increased risk of systemic lupus erythematosus (SLE). Ann Human Genetics 2006;71:308-11.

Biochemistry Basics

Transcription factor: A transcription factor is a protein that works in concert with other proteins to either promote or suppress the process that ultimately leads to the translation of the genetic code into a functional protein. Hence, transcription factors control when and where genes (and the proteins encoded by those genes) are expressed.

Genotype: A genotype is the entire genetic identity of an individual, including alleles that do not show as outward characteristics. Genotyping is the process of determining the genotype of an individual.

Allele: An allele is any one of a number of DNA codings that occupies a specific position on a specific chromosome. Alleles represent variations between different individuals of particular genes.

Proinflammatory cytokines: Cytokines are signaling proteins that are used to allow one cell to communicate with another. Proinflammatory cytokines are those cytokines that induce and perpetuate an inflammatory reaction.

Etiopathogenesis: The cause and development of a disease or abnormal condition is called its etiopathogenesis.