The role of genetic variation near interferon-kappa in systemic lupus erythematosus.

Abstract

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 x 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.

• Authors: Isaac T W Harley, Timothy B Niewold, Rebecca M Stormont, Kenneth M Kaufman, Stuart B Glenn, Beverly S Franek, Jennifer A Kelly, Jeffrey R Kilpatrick, David Hutchings, Jasmin Divers, Gail R Bruner, Jeffrey C Edberg, Gerald McGwin Jr, Michelle A Petri, Rosalind Ramsey-Goldman, John D Reveille, Luis M Vilá-Pérez, Joan T Merrill, Gary S Gilkeson, Timothy J Vyse, Marta E Alarcón-Riquelme, Soo-Kyung Cho, Chaim O Jacob, Graciela S Alarcón, Kathy L Moser, Patrick M Gaffney, Robert P Kimberly, Sang-Cheol Bae, Carl D Langefeld, John B Harley, Joel M Guthridge, Judith A James
• Journal: Journal of biomedicine & biotechnology (J Biomed Biotechnol) Vol. 2010 ( 2010) ISSN: 1110-7251 [Electronic] United States
• PMID: 20706608 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Interferon Type I
• interferon kappa

Topics

• Case-Control Studies
• Chi-Square Distribution
• Female
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• Interferon Type I (genetics)
• Linkage Disequilibrium
• Lupus Erythematosus, Systemic (blood, genetics)
• Male
• Phenotype
• Polymorphism, Single Nucleotide
• Sex Factors
• Skin Physiological Phenomena
• Statistics, Nonparametric