The Role of Genetic Variation Near Interferon-Kappa in Systemic Lupus Erythematosus

Abstract EN

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by increased type I interferons (IFNs) and multiorgan inflammation frequently targeting the skin.

IFN-kappa is a type I IFN expressed in skin.

A pooled genome-wide scan implicated the IFNK locus in SLE susceptibility.

We studied IFNK single nucleotide polymorphisms (SNPs) in 3982 SLE cases and 4275 controls, composed of European (EA), African-American (AA), and Asian ancestry.

rs12553951C was associated with SLE in EA males (odds ratio=1.93, P=2.5×10−4), but not females.

Suggestive associations with skin phenotypes in EA and AA females were found, and these were also sex-specific.

IFNK SNPs were associated with increased serum type I IFN in EA and AA SLE patients.

Our data suggest a sex-dependent association between IFNK SNPs and SLE and skin phenotypes.

The serum IFN association suggests that IFNK variants could influence type I IFN producing plasmacytoid dendritic cells in affected skin.