By pooling results from the three studies, investigators identified 14 common variants in 10 different gene regions (some regions had more than one variant) that were related to QT interval duration. A separate companion paper from the QTSCD consortium in the same issue of Nature Genetics led by Arne Pfeufer, MD, of the Technical University of Munich and Aravinda Chakravarti, PhD, Johns Hopkins University School of Medicine included more than 15,000 individuals from Europe and the US. This independent study strongly confirmed 12 out of 14 of the QTGEN variants and identified two additional gene regions. "We were very reassured to see such strong replication in two independent studies" said Newton-Cheh.
The QTGEN investigators examined the effect of a genotype score comprised of all 14 variants tested together. The top 20 percent of the population with the highest genotype scores had 160 to 210 percent higher risk of prolonged QT interval compared to the 20 percent of the population with the lowest scores. They also had around 10 millisecond longer QT intervals, which is approximately the degree of QT interval prolongation observed for some drugs pulled from the market for arrhythmias.
"While it is commonly a combination of risk factors that contributes to drug-induced arrhythmias such as older age, female sex, use of other medications, or heart disease it is certainly possible that common genetic variants will add incrementally to risk prediction," said Newton-Cheh. "It's currently premature to advocate screening gene variants for risk assessment, but someday it may be possible to identify individuals who are at particularly high risk and should avoid such medications."
Newton-Cheh adds, "It's likely that many more genes will be found to contribute to changes in QT interval, and the real challenge will be understanding the mechanism behind their effects. Five of the gene regions we identified had never be
|Contact: Jennifer Gundersen|
Massachusetts General Hospital