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February 19, 2002Circulation398 citations

Increased Risk of Arrhythmic Events in Long-QT Syndrome With Mutations in the Pore Region of the Human Ether-a-go-go–Related Gene Potassium Channel

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Why the study?

Do mutations in the pore region of the HERG channel increase the risk of arrhythmia-related cardiac events compared to nonpore mutations in patients with LQT2?

Population

201 subjects with the LQT2 form of hereditary long-QT syndrome (44 different HERG mutations)

Comparison

Mutations in the pore region of the HERG channel vs Mutations in nonpore regions of the HERG channel

Design

Cohort

Follow-up

through age 40 years

Key result

Mutations in the pore region of the HERG gene were associated with a markedly higher frequency of arrhythmia-related cardiac events compared with nonpore mutations (74% vs 35%; P<0.001).

Authors

AMArthur J. MossWZWojciech ZarębaEKElizabeth S. Kaufman

Discussion

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Overview

May inform LQT2 risk stratification by mutation site; extends genotype-phenotype data but remains hypothesis-generating.

Study Design

Type

Cohort (n=201)

Structured PICO

Do mutations in the pore region of the HERG channel increase the risk of arrhythmia-related cardiac events compared to nonpore mutations in patients with LQT2?

P
Population
201 subjects with the LQT2 form of hereditary long-QT syndrome (44 different HERG mutations)
I
Intervention
Mutations in the pore region of the HERG channel (amino acid residues 550 through 650)
C
Comparator
Mutations in nonpore regions of the HERG channel
O
Outcome
Arrhythmia-related cardiac eventshard clinical

Patients with LQT2 and mutations in the pore region of the HERG gene are at a markedly increased risk for arrhythmia-related cardiac events compared to those with nonpore mutations.

Main Result

Effect estimate: HR 11

Absolute Event Rate: 74% vs 35%

p-value: p=<0.001

Cite This Study

Moss et al. (2002) conducted a cohort in Long-QT Syndrome (LQT2) (n=201). HERG channel pore region mutations vs. HERG channel nonpore region mutations was evaluated on Arrhythmia-related cardiac events (HR 11, p=<0.001). Mutations in the pore region of the HERG gene were associated with a markedly higher frequency of arrhythmia-related cardiac events compared with nonpore mutations (74% vs 35%; P<0.001).

synapsesocial.com/papers/6a0f47e201be78fe815fa044https://doi.org/10.1161/hc0702.105124
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