title: Genetic variants in interferon regulatory factor 2 (IRF2) are associated with atopic dermatitis and eczema herpeticum.
abstract: Interferon regulatory factor 2 (IRF2) is a member of a family of transcriptional factors involved in the modulation of IFN-induced immune responses to viral infection. To test whether genetic variants in IRF2 predict risk of atopic dermatitis (AD) and ADEH (atopic dermatitis complicated by eczema herpeticum), we genotyped 78 IRF2 tagging single-nucleotide polymorphisms (SNPs) in both European-American (n = 435) and African-American (n = 339) populations. Significant associations were observed between AD and two SNPs (rs793814, P = 0.007, odds ratio (OR) = 0.52; rs3756094, P = 0.037, OR = 0.66) among European Americans and one SNP (rs3775572, P = 0.016, OR = 0.46) among African Americans. Significant associations were also observed between ADEH and five SNPs (P = 0.049-0.022) among European Americans. The association with ADEH was further strengthened by haplotype analyses, wherein a five-SNP (CAGGA) haplotype showed the strongest association with ADEH (P = 0.0008). Eight IRF2 SNPs were significantly associated with IFN-γ production after herpes simplex virus (HSV) stimulation (P = 0.048-0.0008), including an AD-associated SNP (rs13139310, P = 0.008). Our findings suggest that distinct markers in IRF2 may be associated with AD and ADEH, which may depend upon ethnic ancestry, and genetic variants in IRF2 may contribute to an abnormal immune response to HSV.
authors: Department of Medicine, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University, Baltimore, Maryland 21224, USA.
authors: Pei-Song
authors: PS
authors: Gao
authors: Donald Y M
authors: DY
authors: Leung
authors: Nicholas M
authors: NM
authors: Rafaels
authors: Mark
authors: M
authors: Boguniewicz
authors: Tracey
authors: T
authors: Hand
authors: Li
authors: L
authors: Gao
authors: Tissa R
authors: TR
authors: Hata
authors: Lynda C
authors: LC
authors: Schneider
authors: Jon M
authors: JM
authors: Hanifin
authors: Terri H
authors: TH
authors: Beaty
authors: Lisa A
authors: LA
authors: Beck
authors: Adriana
authors: A
authors: Weinberg
authors: Kathleen C
authors: KC
authors: Barnes
mesh_terms: D044383:Black People / Q000235:genetics / Q000706:statistics & numerical data; D003876:Dermatitis, Atopic / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D050836:Interferon Regulatory Factor-2 / Q000235:genetics*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007617:Kaposi Varicelliform Eruption / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018139:Simplexvirus / Q000276:immunology; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data; D001741:Black or African American
chemical_list: C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; D007371:Interferon-gamma