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Title: Gender and effects of a common genetic variant in the NOS1 regulator NOS1AP on cardiac repolarization in 3761 individuals from two independent populations
Authors: Tobin, Martin D.
Kähönen, Mika
Braund, Peter S.
Nieminen, Tuomo
Hajat, Cother
Tomaszewski, Maciej
Viik, Jari
Lehtinen, Rami
Ng, G. Andre
Macfarlane, Peter W.
Burton, Paul R.
Lehtimäki, Terho
Samani, Nilesh J.
First Published: Oct-2008
Publisher: Oxford University Press (OUP)
Citation: International Journal of Epidemiology, 2008, 37 (5), pp. 1132-1141.
Abstract: Background - A longer heart-rate corrected QT interval (QTc) is associated with increased risk of ventricular arrhythmias. Women have longer resting QTc and are more likely than men to develop drug-induced QT prolongation. Recent studies have shown association between resting QTc and a common variant (rs10494366) of the NOS1 regulator, NOS1AP. We investigated the association between rs10494366 in NOS1AP and QTc, and assessed gender-specific NOS1AP associations with QTc during rest and after exercise. Methods - We investigated the SNP associations with resting QTc in 919 women and 918 men from 504 representative families in the UK GRAPHIC study, and with QTc at rest and at 3 min recovery after exercise in 699 women and 1225 men referred for exercise testing in the Finnish FINCAVAS study. Results - In the GRAPHIC study the minor allele (G) of the NOS1AP SNP rs10494366 prolonged QTc by 4.59 ms (95% CI 2.77–6.40; P = 7.63/107) in women, but only by 1.62 ms (95% CI –0.15 to 3.38; P = 0.073) in men (gender-SNP interaction term P = 0.025). In the FINCAVAS study the G allele significantly prolonged QTc in both women (P = 0.0063) and men (P = 0.0043) at 3 min recovery after exercise, but at rest an association was only seen in women (P = 0.020 excluding outliers). Conclusions - A common NOS1AP variant prolongs QTc with a difference between genders. Further studies should aim to confirm this finding and to assess whether NOS1AP genotype influences the risk of drug-induced QT prolongation and risk of consequent arrhythmias.
ISSN: 0300-5771
Type: Article
Description: This paper was published as International Journal of Epidemiology, 2008, 37 (5), pp. 1132-1141. It is available from Doi: 10.1093/ije/dyn091
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Appears in Collections:Published Articles, Dept. of Health Sciences

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