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Mutations in Cytopl...
Mutations in Cytoplasmic Loops of the KCNQ1 Channel and the Risk of Life-Threatening Events Implications for Mutation-Specific Response to beta-Blocker Therapy in Type 1 Long-QT Syndrome
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Barsheshet, Alon (författare)
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Goldenberg, Ilan (författare)
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O-Uchi, Jin (författare)
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visa fler...
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Moss, Arthur J. (författare)
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Jons, Christian (författare)
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Shimizu, Wataru (författare)
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Wilde, Arthur A. (författare)
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McNitt, Scott (författare)
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Peterson, Derick R. (författare)
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Zareba, Wojciech (författare)
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Robinson, Jennifer L. (författare)
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Ackerman, Michael J. (författare)
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Cypress, Michael (författare)
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Gray, Daniel A. (författare)
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Hofman, Nynke (författare)
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Kanters, Jorgen K. (författare)
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Kaufman, Elizabeth S. (författare)
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- Platonov, Pyotr (författare)
- Lund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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Qi, Ming (författare)
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Towbin, Jeffrey A. (författare)
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Vincent, G. Michael (författare)
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Lopes, Coeli M. (författare)
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(creator_code:org_t)
- 2012
- 2012
- Engelska.
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Ingår i: Circulation. - 1524-4539. ; 125:16, s. 1988-1988
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background-beta-Adrenergic stimulation is the main trigger for cardiac events in type 1 long-QT syndrome (LQT1). We evaluated a possible association between ion channel response to beta-adrenergic stimulation and clinical response to beta-blocker therapy according to mutation location. Methods and Results-The study sample comprised 860 patients with genetically confirmed mutations in the KCNQ1 channel. Patients were categorized into carriers of missense mutations located in the cytoplasmic loops (C loops), membrane-spanning domain, C/N terminus, and nonmissense mutations. There were 27 aborted cardiac arrest and 78 sudden cardiac death events from birth through 40 years of age. After multivariable adjustment for clinical factors, the presence of C-loop mutations was associated with the highest risk for aborted cardiac arrest or sudden cardiac death (hazard ratio versus nonmissense mutations = 2.75; 95% confidence interval, 1.29-5.86; P=0.009). beta-Blocker therapy was associated with a significantly greater reduction in the risk of aborted cardiac arrest or sudden cardiac death among patients with C-loop mutations than among all other patients (hazard ratio=0.12; 95% confidence interval, 0.02-0.73; P=0.02; and hazard ratio=0.82; 95% confidence interval, 0.31-2.13; P=0.68, respectively; P for interaction=0.04). Cellular expression studies showed that membrane spanning and C-loop mutations produced a similar decrease in current, but only C-loop mutations showed a pronounced reduction in channel activation in response to beta-adrenergic stimulation. Conclusions-Patients with C-loop missense mutations in the KCNQ1 channel exhibit a high risk for life-threatening events and derive a pronounced benefit from treatment with beta-blockers. Reduced channel activation after sympathetic activation can explain the increased clinical risk and response to therapy in patients with C-loop mutations. (Circulation. 2012; 125: 1988-1996.)
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- adrenergic beta-antagonists
- ion channels
- long QT syndrome
- mutation
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Barsheshet, Alon
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Goldenberg, Ilan
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O-Uchi, Jin
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Moss, Arthur J.
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Jons, Christian
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Shimizu, Wataru
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visa fler...
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Wilde, Arthur A.
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McNitt, Scott
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Peterson, Derick ...
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Zareba, Wojciech
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Robinson, Jennif ...
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Ackerman, Michae ...
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Cypress, Michael
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Gray, Daniel A.
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Hofman, Nynke
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Kanters, Jorgen ...
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Kaufman, Elizabe ...
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Platonov, Pyotr
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Qi, Ming
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Towbin, Jeffrey ...
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Vincent, G. Mich ...
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Lopes, Coeli M.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
- Artiklar i publikationen
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Circulation
- Av lärosätet
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Lunds universitet