Common variation in NOS1AP and KCNH2 genes and QT interval duration in young adults. The Cardiovascular Risk in Young Finns Study

Background: Common genetic variants in the nitric oxide synthase 1 adaptor protein gene (NOS1AP) and in the HERG potassium channel gene (KCNH2) have been associated with cardiac repolarization in middle-aged and elderly subjects. Aim: We examined the relation between these variants and QT interval duration in a population of healthy young adults. Methods: We measured QT interval duration and genotyped rs10494366 TG (NOS1AP gene, n=1,842) and rs1805123 AC (KCNH2 gene, n=1,894) in subjects aged 24-39 years. Results: The NOS1AP variant was significantly related with heart rate-corrected QT interval duration (QTc). Additive regression model adjusting for age, sex, systolic blood pressure, body mass index, alcohol use, and smoking indicated that the G allele was associated with a 3.2 ms (95% confidence interval (CI) 1.7-4.6 ms, P0.0001) increase in QTc interval duration for each additional copy. The KCNH2 variant was not significantly related with QTc interval duration in the study sample. Conclusion: These findings provide evidence from a population of healthy young adults that a common variation in the NOS1AP gene influences cardiac repolarization within the normal physiological range. Further studies are warranted to investigate the effects of this variant on sudden cardiac death and ventricular arrhythmias.