Escitalopram-induced QTc prolongation and its relationship with KCNQ1,
KCNE1, and KCNH2 gene polymorphisms
Abstract
Aims: We investigated the influence of KCNQ1, KCNE1, and KCNH2 gene
polymorphisms along with clinical factors on escitalopram-induced QTc
prolongation. Methods: A total of 713 patients prescribed escitalopram
were identified and had at least one ECG recording in this retrospective
study. 472 patients with two or more ECG data were divided into QTc
prolongation (n=119) and non-prolongation (n=353) groups depending on
the threshold change in QTc of 30ms above baseline value (∆QTc≥30ms). 45
patients in the QTc prolongation group and 90 patients in the QTc
non-prolongation group were genotyped for 43 single nucleotide
polymorphisms (SNPs) of KCNQ1, KCNE1, and KCNH2 genes. Results: Patients
with QTc prolongation (∆QTc≥30ms) still got higher escitalopram dose
(10.3mg) than patients without QTc prolongation (9.4mg), although no
significant relationship was found between QTc interval and escitalopram
dose among all patients. Patients who were older, or with coronary
disease, or with hypertension were significantly at risk for QTc
prolongation (∆QTc≥30ms). Concomitant antipsychotic treatment was
associated with a longer QTc interval (7.469ms). Additionally, the
distribution of KCNE1 rs1805127 C allele, KCNE1 rs4817668 CC genotype
KCNH2 rs3807372 AG genotype differed significantly between the QTc
prolongation and non-prolongation groups. Conclusion: Patients with QTc
prolongation got higher escitalopram dose. Meanwhile, Greater age,
coronary disease and hypertension are risk factors for QTc prolongation.
Patients prescribed escitalopram would have longer QTc interval when
prescribed concomitant antipsychotics at the same time. Moreover,
polymorphism of KCNE1 and KCNH2 SNPs play a role in escitalopram-induced
QTc prolongation.