TY - JOUR
T1 - Genetic variants in interferon regulatory factor 2 (IRF2) are associated with atopic dermatitis and eczema herpeticum
AU - Gao, Pei Song
AU - Leung, Donald Y.M.
AU - Rafaels, Nicholas M.
AU - Boguniewicz, Mark
AU - Hand, Tracey
AU - Gao, Li
AU - Hata, Tissa R.
AU - Schneider, Lynda C.
AU - Hanifin, Jon M.
AU - Beaty, Terri H.
AU - Beck, Lisa A.
AU - Weinberg, Adriana
AU - Barnes, Kathleen C.
N1 - Funding Information:
We acknowledge several groups without whom this study would not have been possible: ADVN coordinators (Patricia Taylor, Trista Berry, Susan Tofte, Shahana Baig-Lewis, Peter Brown, Lisa Heughan, Meggie Nguyen, Doru Alexandrescu, Lorianne Stubbs, Deborra James, Reena Vaid, and Diana Lee), ADVN regulatory advisers (Judy Lairsmith and Lisa Leventhal), biological sample tracking (Jessica Scarpola, Muralidhar Bopparaju, Mary Bolognino, and Lisa Latchney), NIAID-DAIT support (Marshall Plaut and Joy Laurienzo Panza), DACI Laboratory (Robert Hamilton), and all of the patients who participated in this study. A special thanks to Daniel Zaccaro, Jamie Reese, and Susan Lieff at Rho for coordination of the study; Rasika Mathias (JHAAC) for her critical comments; and Patricia Oldewurtel (JHAAC) and Maureen Sandoval (NJH) for technical assistance. This research was supported by the Atopic Dermatitis and Vaccinia Network NIH/NIAID contracts HHSN266200400029C and HHSN266200400033C. KCB was supported in part by the Mary Beryl Patch Turnbull Scholar Program.
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
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U2 - 10.1038/jid.2011.374
DO - 10.1038/jid.2011.374
M3 - Article
C2 - 22113474
AN - SCOPUS:84857052949
SN - 0022-202X
VL - 132
SP - 650
EP - 657
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 3 PART 1
ER -