Details

Autor(en) / Beteiligte

• Esparza-Gordillo, Jorge, PhD
• Schaarschmidt, Heidi, ME
• Liang, Liming, PhD
• Cookson, William, MD, DPhil
• Bauerfeind, Anja, PhD
• Lee-Kirsch, Min-Ae, MD
• Nemat, Katja, MD
• Henderson, John, MD
• Paternoster, Lavinia, PhD
• Harper, John I., MD
• Mangold, Elisabeth, MD
• Nothen, Markus M., MD
• Rüschendorf, Franz, PhD
• Kerscher, Tamara, PhD
• Marenholz, Ingo, PhD
• Matanovic, Anja, MSc
• Lau, Susanne, MD
• Keil, Thomas, MD, MSc
• Bauer, Carl-Peter, MD
• Kurek, Michael, MD
• Ciechanowicz, Andrzej, MD
• Macek, Milan, MD, DSc
• Franke, Andre, PhD
• Kabesch, Michael, MD
• Hubner, Norbert, MD
• Abecasis, Gonçalo, PhD
• Weidinger, Stephan, MD
• Moffatt, Miriam, DPhil
• Lee, Young-Ae, MD

Titel

A functional IL-6 receptor ( IL6R ) variant is a risk factor for persistent atopic dermatitis

Ist Teil von

• Journal of allergy and clinical immunology, 2013-08, Vol.132 (2), p.371-377

Ort / Verlag

New York, NY: Mosby, Inc

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Background Atopic dermatitis (AD) is a common inflammatory skin disease. Previous studies have revealed shared genetic determinants among different inflammatory disorders, suggesting that markers associated with immune-related traits might also play a role in AD. Objective We sought to identify novel genetic risk factors for AD. Methods We examined the results of all genome-wide association studies from a public repository and selected 318 genetic markers that were significantly associated with any inflammatory trait. These markers were considered candidates and tested for association with AD in a 3-step approach including 7 study populations with 7130 patients with AD and 9253 control subjects. Results A functional amino acid change in the IL-6 receptor (IL-6R Asp358Ala; rs2228145) was significantly associated with AD (odds ratio [OR], 1.15; P  = 5 × 10−9 ). Interestingly, investigation of 2 independent population-based birth cohorts showed that IL-6R 358Ala specifically predisposes to the persistent form of AD (ORpersistent AD  = 1.22, P  = .0008; ORtransient AD  = 1.04, P  = .54). This variant determines the balance between the classical membrane-bound versus soluble IL-6R signaling pathways. Carriers of 358Ala had increased serum levels of soluble IL-6R ( P  = 4 × 10−14 ), with homozygote carriers showing a 2-fold increase. Moreover, we demonstrate that soluble IL-6R levels were higher in patients with AD than in control subjects (46.0 vs 37.8 ng/mL, P  = .001). Additional AD risk variants were identified in RAD50 , RUNX3 , and ERBB3. Conclusion Our study supports the importance of genetic variants influencing inflammation in the etiology of AD. Moreover, we identified a functional genetic variant in IL6R influencing disease prognosis and specifically predisposing to persistent AD.