The role of genetic variation near interferon-kappa in systemic lupus erythematosus.
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.
Harley
Isaac T W
IT
Division of Molecular Immunology and Graduate Program in Immunobiology, Cincinnati Children's Hospital Research Foundation, OH 45267, USA.
Niewold
Timothy B
TB
Stormont
Rebecca M
RM
Kaufman
Kenneth M
KM
Glenn
Stuart B
SB
Franek
Beverly S
BS
Kelly
Jennifer A
JA
Kilpatrick
Jeffrey R
JR
Hutchings
David
D
Divers
Jasmin
J
Bruner
Gail R
GR
Edberg
Jeffrey C
JC
McGwin
Gerald
G
Petri
Michelle A
MA
Ramsey-Goldman
Rosalind
R
Reveille
John D
JD
Vilá-Pérez
Luis M
LM
Merrill
Joan T
JT
Gilkeson
Gary S
GS
Vyse
Timothy J
TJ
Alarcón-Riquelme
Marta E
ME
Cho
Soo-Kyung
SK
Jacob
Chaim O
CO
Alarcón
Graciela S
GS
Moser
Kathy L
KL
Gaffney
Patrick M
PM
Kimberly
Robert P
RP
Bae
Sang-Cheol
SC
Langefeld
Carl D
CD
Harley
John B
JB
Guthridge
Joel M
JM
James
Judith A
JA
D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D012879:Skin Physiological Phenomena; D018709:Statistics, Nonparametric
D007370:Interferon Type I; C439669:interferon kappa