Gender and effects of a common genetic variant in the NOS1 regulator NOS1AP on cardiac repolarization in 3761 individuals from two independent populations
| Autor: | Jari Viik, Cother Hajat, Peter W. Macfarlane, Nilesh J. Samani, G. André Ng, Maciej Tomaszewski, Peter S. Braund, Mika Kähönen, Tuomo Nieminen, Martin D. Tobin, Paul Burton, Terho Lehtimäki, Rami Lehtinen |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male medicine.medical_specialty Genotype Epidemiology Long QT syndrome Population Single-nucleotide polymorphism Electrocardiography Sex Factors Heart Rate NOS1AP Internal medicine Genetic variation medicine Humans Allele education Exercise Alleles Finland Adaptor Proteins Signal Transducing Genetic association Genetics education.field_of_study business.industry Genetic Variation Heart General Medicine Middle Aged medicine.disease Health Surveys United Kingdom Long QT Syndrome Endocrinology Linear Models Female business |
| Zdroj: | International Journal of Epidemiology. 37:1132-1141 |
| ISSN: | 1464-3685 0300-5771 |
| DOI: | 10.1093/ije/dyn091 |
| Popis: | 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.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.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 = 7.63/10(7)) 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).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. |
| Databáze: | OpenAIRE |
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