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Common variation ne...
Common variation near IRF6 is associated with IFN-beta-induced liver injury in multiple sclerosis
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- Kowalec, Kaarina (författare)
- Karolinska Institutet,Univ British Columbia, Div Neurol, Fac Med, Vancouver, BC, Canada;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Univ British Columbia, Div Translat Therapeut, Dept Pediat, Vancouver, BC, Canada
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- Wright, Galen E. B. (författare)
- Univ British Columbia, Div Translat Therapeut, Dept Pediat, Vancouver, BC, Canada;British Columbia Childrens Hosp Res Inst, Vancouver, BC, Canada;Univ British Columbia, Dept Med Genet, Fac Med, Vancouver, BC, Canada
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- Drogemoller, Britt I. (författare)
- Univ British Columbia, Div Translat Therapeut, Dept Pediat, Vancouver, BC, Canada;British Columbia Childrens Hosp Res Inst, Vancouver, BC, Canada;Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC, Canada
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- Aminkeng, Folefac (författare)
- Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore, Singapore;Agcy Sci Res & Technol, Translat Lab Genet Med, Singapore, Singapore
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- Bhavsar, Amit P. (författare)
- British Columbia Childrens Hosp Res Inst, Vancouver, BC, Canada;Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC, Canada;Univ Alberta, Fac Med & Dent, Dept Med Microbiol & Immunol, Edmonton, AB, Canada
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- Kingwell, Elaine (författare)
- Univ British Columbia, Div Neurol, Fac Med, Vancouver, BC, Canada
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- Yoshida, Eric M. (författare)
- Univ British Columbia, Div Gastroenterol, Fac Med, Vancouver, BC, Canada
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- Traboulsee, Anthony (författare)
- Univ British Columbia, Div Neurol, Fac Med, Vancouver, BC, Canada
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- Marrie, Ruth Ann (författare)
- Univ Manitoba, Rady Fac Hlth Sci, Max Rady Coll Med, Dept Internal Med, Winnipeg, MB, Canada;Univ Manitoba, Rady Fac Hlth Sci, Max Rady Coll Med, Dept Community Hlth Sci, Winnipeg, MB, Canada
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- Kremenchutzky, Marcelo (författare)
- Western Univ, Fac Med, London Hlth Sci Ctr, London, ON, Canada;Western Univ, Fac Med, Dept Clin Neurol Sci, London, ON, Canada
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- Campbell, Trudy L. (författare)
- Dalhousie Univ, Dalhousie Multiple Sclerosis Res Uni, Halifax, NS, Canada;Dalhousie Univ, Sch Nursing, Halifax, NS, Canada
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- Duquette, Pierre (författare)
- Univ Montreal, Dept Neurosci, Montreal, PQ, Canada
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- Chalasani, Naga (författare)
- Indiana Univ Sch Med, Div Gastroenterol Hepatol, Indianapolis, IN 46202 USA
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- Wadelius, Mia (författare)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab
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- Hallberg, Pär, 1974- (författare)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab
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- Xia, Zongqi (författare)
- Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA
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- De Jager, Philip L. (författare)
- Columbia Univ, Med Ctr, Dept Neurol, Ctr Translat & Computat Neuroimmunol, New York, NY USA.;Columbia Univ, Med Ctr, Dept Neurol, Multiple Sclerosis Ctr, New York, NY USA.;Broad Inst, Cambridge, MA USA
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- Denny, Joshua C. (författare)
- Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA.;Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA,British Columbia Childrens Hosp Res Inst, Vancouver, BC, Canada.;Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC, Canada
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- Davis, Mary F. (författare)
- Brigham Young Univ, Dept Microbiol & Mol Biol, Provo, UT 84602 USA
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- Ross, Colin J. D. (författare)
- British Columbia Childrens Hosp Res Inst, Vancouver, BC, Canada.;Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC, Canada
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- Tremlett, Helen (författare)
- Univ British Columbia, Div Neurol, Fac Med, Vancouver, BC, Canada
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- Carleton, Bruce C. (författare)
- Univ British Columbia, Div Translat Therapeut, Dept Pediat, Vancouver, BC, Canada.;British Columbia Childrens Hosp Res Inst, Vancouver, BC, Canada
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(creator_code:org_t)
- 2018-07-16
- 2018
- Engelska.
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:8, s. 1081-
- Relaterad länk:
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Multiple sclerosis (MS) is a disease of the central nervous system treated with disease-modifying therapies, including the biologic, interferon-β (IFN-β). Up to 60% of IFN-β-exposed MS patients develop abnormal biochemical liver test results1,2, and 1 in 50 experiences drug-induced liver injury3. Since genomic variation contributes to other forms of drug-induced liver injury4,5, we aimed to identify biomarkers of IFN-β-induced liver injury using a two-stage genome-wide association study. The rs2205986 variant, previously linked to differential expression of IRF6, surpassed genome-wide significance in the combined two-stage analysis (P = 2.3 × 10–8, odds ratio = 8.3, 95% confidence interval = 3.6–19.2). Analysis of an independent cohort of IFN-β-treated MS patients identified via electronic medical records showed that rs2205986 was also associated with increased peak levels of aspartate aminotransferase (P = 7.6 × 10–5) and alkaline phosphatase (P = 4.9 × 10-4). We show that these findings may be applicable to predicting IFN-β-induced liver injury, offering insight into its safer use.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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Kowalec, Kaarina
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Wright, Galen E. ...
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Drogemoller, Bri ...
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Aminkeng, Folefa ...
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Bhavsar, Amit P.
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Kingwell, Elaine
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Yoshida, Eric M.
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Traboulsee, Anth ...
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Marrie, Ruth Ann
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Kremenchutzky, M ...
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Campbell, Trudy ...
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Duquette, Pierre
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Chalasani, Naga
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Wadelius, Mia
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Hallberg, Pär, 1 ...
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Xia, Zongqi
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De Jager, Philip ...
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Denny, Joshua C.
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Davis, Mary F.
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Ross, Colin J. D ...
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Tremlett, Helen
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Carleton, Bruce ...
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Nature Genetics
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Uppsala universitet
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Karolinska Institutet