PuSH - Publikationsserver des Helmholtz Zentrums München

de Villiers, C.P.* ; van der Merwe, L.* ; Crotti, L. ; Goosen, A.* ; George, A.L. Jr.* ; Schwartz, P.J.* ; Brink, P.A.* ; Moolman-Smook, J.C.* ; Corfield, V.A.*

AKAP9 is a genetic modifier of congenital long-QT syndrome type 1.

Circ. Cardiovasc. Genet. 7, 599-606 (2014)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
BACKGROUND: -Long-QT syndrome (LQTS), a cardiac arrhythmia disorder with variable phenotype, often results in devastating outcomes including sudden cardiac death. Variable expression, independently from the primary disease-causing mutation, can partly be explained by genetic modifiers. This study investigates variants in a known LQTS-causative gene, AKAP9, for potential LQTS-type 1 (LQT1) modifying effects. METHODS AND RESULTS: -Members of a South African LQT1 founder population (181 non-carriers and 168 mutation carriers) carrying the identical-by-descent KCNQ1 p.Ala341Val (A341V) mutation were evaluated for modifying effects of AKAP9 variants on heart rate-corrected QT interval (QTc), cardiac events and disease severity. Tag single nucleotide polymorphisms in AKAP9 rs11772585, rs7808587, rs2282972 and rs2961024 (order: 5'- 3'positive strand) were genotyped. Associations between phenotypic traits and alleles, genotypes and haplotypes were statistically assessed, adjusting for the degree of relatedness and confounding variables. The rs2961024 GG genotype, always represented by CGCG haplotype homozygotes, revealed an age-dependent QTc increase (1% per additional 10 years) irrespective of A341V mutation status (P=0.006). The rs11772585 T allele, found uniquely in the TACT haplotype, more than doubled (218%) the risk of cardiac events (P=0.002), in the presence of A341V; additionally, it increased disease severity (P=0.025). The rs7808587 GG genotype was associated with a 74% increase in cardiac event risk (P=0.046), while the rs2282972 T allele, predominantly represented by the CATT haplotype, decreased risk by 53% (P=0.001). CONCLUSIONS: -AKAP9 has been identified as a LQT1-modifying gene. Variants investigated altered QTc irrespective of mutation status, as well as cardiac event risk, and disease severity, in mutation carriers.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Akap9 ; Kcnq1 ; Arrhythmia ; Long Qt Syndrome
ISSN (print) / ISBN 1942-325X
e-ISSN 1942-3268
Zeitschrift Circulation: Cardiovascular Genetics
Quellenangaben Band: 7, Heft: 5, Seiten: 599-606 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Hagerstown, Md
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)