Résumé :
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[BDSP. Notice produite par INIST-CNRS Dk79DR0x. Diffusion soumise à autorisation]. 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 rsl0494366 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 1.62ms (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.
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