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Duchatelet, S.* ; Crotti, L. ; Peat, R.A.* ; Denjoy, I.* ; Itoh, H.* ; Berthet, M.* ; Ohno, S.* ; Fressart, V.* ; Monti, M.C.* ; Crocamo, C.* ; Pedrazzini, M.* ; Dagradi, F.* ; Vicentini, A.* ; Klug, D.* ; Brink, P.A.* ; Goosen, A.* ; Swan, H.* ; Toivonen, L.* ; Lahtinen, A.M.* ; Kontula, K.* ; Shimizu, W.* ; Horie, M.* ; George, A.L.* ; Tregouet, D.A.* ; Guicheney, P.* ; Schwartz, P.J.*

Identification of a KCNQ1 polymorphism acting as a protective modifier against arrhythmic risk in long-QT syndrome.

Circ. Cardiovasc. Genet. 6, 354-361 (2013)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Background Long-QT syndrome (LQTS) is characterized by such striking clinical heterogeneity that, even among family members carrying the same mutation, clinical outcome can range between sudden death and no symptoms. We investigated the role of genetic variants as modifiers of risk for cardiac events in patients with LQTS. Methods and Results In a matched case-control study including 112 patient duos with LQTS from France, Italy, and Japan, 25 polymorphisms were genotyped based on either their association with QTc duration in healthy populations or on their role in adrenergic responses. The duos were composed of 2 relatives harboring the same heterozygous KCNQ1 or KCNH2 mutation: 1 with cardiac events and 1 asymptomatic and untreated. The findings were then validated in 2 independent founder populations totaling 174 symptomatic and 162 asymptomatic patients with LQTS, and a meta-analysis was performed. The KCNQ1 rs2074238 T-allele was significantly associated with a decreased risk of symptoms 0.34 (0.19-0.61; P<0.0002) and with shorter QTc (P<0.0001) in the combined discovery and replication cohorts. Conclusions We provide evidence that the KCNQ1 rs2074238 polymorphism is an independent risk modifier with the minor T-allele conferring protection against cardiac events in patients with LQTS. This finding is a step toward a novel approach for risk stratification in patients with LQTS.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Association Studies ; Genetics ; Ion Channel ; Long-qt Syndrome ; Polymorphism ; Risk Factor; Sudden Cardiac Death ; Interval Duration ; Common Variants ; Heart-rate ; Gene ; Population ; Type-1 ; Stratification ; Associations ; Mutation
ISSN (print) / ISBN 1942-325X
e-ISSN 1942-3268
Zeitschrift Circulation: Cardiovascular Genetics
Quellenangaben Band: 6, Heft: 4, Seiten: 354-361 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Hagerstown, Md
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)