Letter by Amin et al Regarding Article, “Genetic Modifiers for the Long-QT Syndrome: How Important Is the Role of Variants in the 3′ Untranslated Region of KCNQ1?”
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
To the Editor:
In their article, Crotti et al1 aimed to replicate our earlier discovery that single-nucleotide polymorphisms (SNPs) in the 3′ untranslated region (3′UTR) of KCNQ1 can suppress gene expression and thereby alter disease expressivity in patients with type 1 long-QT syndrome (LQT1).2 To do this, they studied the association between 3 3′UTR SNPs and the clinical phenotype in 3 LQT1 founder populations. They found that the 3′UTR SNPs were not associated with QTc or symptoms in these 3 populations. However, when the 3 groups were combined, the derived SNP haplotype located on the mutated allele did associate with shorter QTc and less cardiac events, which is fully in line with our earlier discovery. Despite this clear congruency with our findings, the authors still conclude that they could not replicate our findings. They base this on additional statistical analysis because when they …