Esparza-Gordillo, Jorge and Schaarschmidt, Heidi and Liang, Liming and Cookson, William and Bauerfeind, Anja and Lee-Kirsch, Min-Ae and Nemat, Katja and Henderson, John and Paternoster, Lavinia and Harper, John I. and Mangold, Elisabeth and Nothen, Markus M. and Rueschendorf, Franz and Kerscher, Tamara and Marenholz, Ingo and Matanovic, Anja and Lau, Susanne and Keil, Thomas and Bauer, Carl-Peter and Kurek, Michael and Ciechanowicz, Andrzej and Macek, Milan and Franke, Andre and Kabesch, Michael and Hubner, Norbert and Abecasis, Goncalo and Weidinger, Stephan and Moffatt, Miriam and Lee, Young-Ae (2013) A functional IL-6 receptor (IL6R) variant is a risk factor for persistent atopic dermatitis. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 132 (2). pp. 371-377. ISSN 0091-6749, 1097-6825
Full text not available from this repository. (Request a copy)Abstract
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 x 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 5 4 3 10 214), 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ASTHMA; ASSOCIATION; DISEASE; BIRTH; CHILDHOOD; CHILDREN; ECZEMA; MECHANISMS; MUTATIONS; BURDEN; Atopic dermatitis; persistent atopic dermatitis; prognosis; inflammation; soluble IL-6 receptor; single nucleotide polymorphism; longitudinal study; population-based cohort; candidate association study; genetic risk factor |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Apr 2020 06:20 |
| Last Modified: | 06 Apr 2020 06:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16304 |
Actions (login required)
 |
View Item |
