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.


OBJECTIVE
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 T>G (NOS1AP gene, n=1,842) and rs1805123 A>C (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, P<0.0001) increase in QTc interval duration for each additional copy. The KCNH2 variant was not significantly related with QTc interval duration in the study sample.


CONCLUSIONS
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.
Raitakari
Olli T
OT
Department of Clinical Physiology, University of Turku, Finland. olli.raitakari@utu.fi
Blom-Nyholm
Jaana
J
Koskinen
Tuomas A
TA
Kähönen
Mika
M
Viikari
Jorma S A
JS
Lehtimäki
Terho
T
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D003430:Cross-Sectional Studies; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D005387:Finland; D014644:Genetic Variation; D005838:Genotype; D006329:Heart Conduction System / Q000502:physiology*; D006339:Heart Rate; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016036:Seroepidemiologic Studies; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C488081:NOS1AP protein, human