Arrhythmias & electrophysiologyResearch article
MTMR4 variants have opposite gene-specific impact on life-threatening arrhythmic risk in type 1 and 2 long QT syndrome
- Genetic association study
Authors' conclusion
The MTMR4 minor allele in homozygosis exerts a gene-specific and opposite impact on arrhythmic risk in LQTS.
Study context
- Population
- Patients with LQT1 and LQT2 long QT syndrome, including Swedish carriers of the p.Y111C-LQT1 variant638 LQT1, 432 LQT2, 122 Swedish
- Participants
- 1,192 patients
- Comparison
- MTMR4 genotypes in LQT1 vs LQT2
- Outcome
- Severe symptoms (cardiac arrest or syncope on beta-blockers) vs asymptomatic or mildly symptomatic
Further findings
| Outcome | Values | P value |
|---|---|---|
| aa genotype frequency, severe vs mild/asymptomatic, combined LQT1 cohort | Mild/asymptomatic 15% · Severe symptoms 1.7% | P = 0.002 |
| aa genotype frequency, severe vs mild/asymptomatic, LQT2 | Severe 24.1% · Mild/asymptomatic 11.9% | P = 0.014 |
- aa genotype frequency, severe vs mild/asymptomatic, combined LQT1 cohort: 702 mild/asymptomatic vs 58 severe
QTc and repolarization markers
- QTc not associated with MTMR4; repolarization markers supported gene-specific directionality of arrhythmic risk
Original publication
MTMR4 variants have opposite gene-specific impact on life-threatening arrhythmic risk in type 1 and 2 long QT syndrome. Eur Heart J. Published 13 May 2026. doi:10.1093/eurheartj/ehag294
Summarised from the published abstract; every number is checked against it