Three Susceptibility Loci Confirmed for SLE
IRF8, TMEM39A, and IKZF3-ZPBP2 exceed threshold for genome-wide significance
FRIDAY, March 30 (HealthDay News) -- A large genome-wide association study has replicated three systemic lupus erythematosus (SLE) loci, according to research published online March 29 in the American Journal of Human Genetics.
Christopher J. Lessard, Ph.D., from the Oklahoma Medical Research Foundation in Oklahoma City, and colleagues aimed to replicate 1,580 genetic variants that were previously shown to be associated with SLE in a genome-wide association scan of European Americans. A multiethnic population comprising 7,998 cases of SLE and 7,492 controls was tested to find genetic associations with SLE.
The researchers identified several genes associated with SLE which had relevance to immunological pathways. Interferon regulatory factor 8 (IRF8), transmembrane protein 39A (TMEM39A), and a region of chromosome 17q21 between IKAROS family of zinc finger 3 and zona pellucida binding protein 2 (IKZF3-ZPBP2) exceeded the threshold for genome-wide significance. For individuals of European ancestry, mapping, resequencing, and haplotype analysis of IRF8 indicated that three independent effects tagged by three single nucleotide polymorphisms were required for risk. Eleven additional effects were seen, but these did not reach genome-wide significance.
"In conclusion, we have robustly established three additional susceptibility loci for SLE: IRF8, TMEM39A, and IKZF3-ZPBP2," the authors write. "Eleven other regions were replicated but did not exceed the genome-wide threshold of significance. Collectively, these data, along with other previously reported loci, demonstrate the growing complexity of the heritable contribution to SLE pathogenesis."