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

Circ Cardiovasc Genet 2013 Aug 15;6(4):354-61. Epub 2013 Jul 15.

INSERM, UMR S956, Paris, France.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCGENETICS.113.000023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864834PMC
August 2013
42 Reads

Publication Analysis

Top Keywords

cardiac events
8
long-qt syndrome
8
populations role
4
untreated findings
4
risk cardiac
4
events patients
4
asymptomatic patients
4
symptomatic 162
4
lqtsmethods matched
4
162 asymptomatic
4
patients lqtsmethods
4
kcnh2 mutation
4
modifiers risk
4
investigated role
4
adrenergic responses
4
symptoms investigated
4
responses duos
4
lqts meta-analysis
4
role genetic
4
variants modifiers
4

References

(Supplied by CrossRef)

Similar Publications