Phenotypic variability in Caucasian and Japanese patients with matched LQT1 mutations

Judy F. Liu, Ilan Goldenberg*, Arthur J. Moss, Wataru Shimizu, Arthur A. Wilde, Nynke Hofman, Scott McNitt, Wojciech Zareba, Yoshihiro Miyamato, Jennifer L. Robinson, Mark L. Andrews

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Ethnic differences may affect the phenotypic expression of genetic disorders. However, data regarding the effect of ethnicity on outcome in patients with genetic cardiac disorders are limited. We compared the clinical course of Caucasian and Japanese long QT type-1 (LQT1) patients who were matched for mutations in the KCNQ1 gene. Methods: The study population comprised 62 Caucasian and 38 Japanese LQT1 patients from the International LQTS Registry who were identified as having six identical KCNQ1 mutations. The biophysical function of the mutations was categorized into dominant-negative (>50%) or haploinsufficiency (≤50%) reduction in cardiac repolarizing IKs potassium channel current. The primary end point of the study was the occurrence of a first cardiac event from birth through age 40 years. Results: Japanese patients had a significantly higher cumulative rate of cardiac events (67%) than Caucasian patients (39%; P = 0.01). The respective frequencies of dominant negative mutations in the two ethnic groups were 63% and 28% (P < 0.001). In multivariate analysis, Japanese patients had an 81% increase in the risk of cardiac events (P = 0.06) as compared with Caucasians. However, when the biophysical function of the mutations was included in the multivariate model, the risk associated with Japanese ethnicity was no longer evident (HR = 1.05; P = 0.89). Harboring a dominant negative mutation was shown to be the most powerful and significant predictor of outcome (HR = 3.78; P < 0.001). Conclusions: Our data indicate that ethnic differences in the clinical expression of LQTS can be attributed to the differences in frequencies of the specific mutations within the two populations.

Original languageEnglish
Pages (from-to)234-241
Number of pages8
JournalAnnals of Noninvasive Electrocardiology
Volume13
Issue number3
DOIs
StatePublished - Jul 2008
Externally publishedYes

Funding

FundersFunder number
National Heart, Lung, and Blood InstituteR01HL051618

    Keywords

    • Ethnicity
    • Genetics
    • Long-QT syndrome

    Fingerprint

    Dive into the research topics of 'Phenotypic variability in Caucasian and Japanese patients with matched LQT1 mutations'. Together they form a unique fingerprint.

    Cite this