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| rdfs:seeAlso
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| Description
| - 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.
- 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. (en)
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| Title
| - A functional IL-6 receptor (IL6R) variant is a risk factor for persistent atopic dermatitis
- A functional IL-6 receptor (IL6R) variant is a risk factor for persistent atopic dermatitis (en)
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| skos:prefLabel
| - A functional IL-6 receptor (IL6R) variant is a risk factor for persistent atopic dermatitis
- A functional IL-6 receptor (IL6R) variant is a risk factor for persistent atopic dermatitis (en)
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| skos:notation
| - RIV/00216208:11130/13:10209575!RIV14-MSM-11130___
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| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/00216208:11130/13:10209575
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| http://linked.open...riv/jazykVysledku
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| http://linked.open.../riv/klicovaSlova
| - genetic risk factor; candidate association study; population-based cohort; longitudinal study; single nucleotide polymorphism; soluble IL-6 receptor; inflammation; prognosis; persistent atopic dermatitis; Atopic dermatitis (en)
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| http://linked.open.../riv/klicoveSlovo
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| http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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| http://linked.open...ontrolniKodProRIV
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| http://linked.open...i/riv/nazevZdroje
| - Journal of Allergy and Clinical Immunology
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| http://linked.open...in/vavai/riv/obor
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| http://linked.open...ichTvurcuVysledku
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| http://linked.open...cetTvurcuVysledku
| |
| http://linked.open...UplatneniVysledku
| |
| http://linked.open...v/svazekPeriodika
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| http://linked.open...iv/tvurceVysledku
| - Macek, Milan
- Abecasis, Goncalo
- Bauer, Carl-Peter
- Bauerfeind, Anja
- Ciechanowicz, Andrzej
- Cookson, William
- Esparza-Gordillo, Jorge
- Franke, Andre
- Harper, John I.
- Henderson, John
- Hubner, Norbert
- Kabesch, Michael
- Keil, Thomas
- Kerscher, Tamara
- Kurek, Michael
- Lau, Susanne
- Lee, Young-Ae
- Lee-Kirsch, Min-Ae
- Liang, Liming
- Mangold, Elisabeth
- Marenholz, Ingo
- Matanovic, Anja
- Moffatt, Miriam
- Nemat, Katja
- Nothen, Markus M.
- Paternoster, Lavinia
- Rueschendorf, Franz
- Schaarschmidt, Heidi
- Weidinger, Stephan
|
| http://linked.open...ain/vavai/riv/wos
| |
| issn
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| number of pages
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| http://bibframe.org/vocab/doi
| - 10.1016/j.jaci.2013.01.057
|
| http://localhost/t...ganizacniJednotka
| |
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