2007
DOI: 10.1161/circulationaha.106.676783
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Common NOS1AP Variants Are Associated With a Prolonged QTc Interval in the Rotterdam Study

Abstract: Background-QT prolongation is an important risk factor for sudden cardiac death. About 35% of QT-interval variation is heritable. In a recent genome-wide association study, a common variant (rs10494366) in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene was found to be associated with QT-interval variation. We tested for association of 2 NOS1AP variants with QT duration and sudden cardiac death. Methods and Results-The Rotterdam Study is a population-based, prospective cohort study of individuals Ն55… Show more

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Cited by 128 publications
(102 citation statements)
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References 46 publications
(34 reference statements)
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“…This association was replicated in two other population-based studies (11), an elderly population (12) and the genetically more homogeneous Old Order Amish population (13). However, the propensity for false-positive reports in genetic association studies warrants replication in additional cohorts: especially cohorts with high risk for prolonged QT interval and SCD due to competing factors, such as diabetes and coronary disease.…”
mentioning
confidence: 78%
“…This association was replicated in two other population-based studies (11), an elderly population (12) and the genetically more homogeneous Old Order Amish population (13). However, the propensity for false-positive reports in genetic association studies warrants replication in additional cohorts: especially cohorts with high risk for prolonged QT interval and SCD due to competing factors, such as diabetes and coronary disease.…”
mentioning
confidence: 78%
“…NOS1AP variants have been shown to be strongly associated with the QT interval and the risk of sudden cardiac death in elderly Hollanders (Aarnoudse et al, 2007), the South African LQTS population (Crotti et al, 2009), and the Rotterdam Study (Eijgelsheim et al, 2009a(Eijgelsheim et al, , 2009b. Interestingly, two independent studies have confirmed that an NOS1AP variant is associated with the QT interval duration in Chinese (Lu et al, 2010;Qin et al, 2010).…”
Section: Discussionmentioning
confidence: 99%
“…10 SNPs selection and analysis. Candidate single nucleotide polymorphisms (SNPs) were selected among those previously described as modulating ECG intervals [11][12][13][14][15][16][17] or predisposition to arrhythmic events. [18][19][20][21][22][23][24][25][26][27][28][29][30][31] In particular, most variants were located in genes encoding cardiac voltage-dependent channels (KCNQ1, KCNH2, SCN5A, KCNJ11, KCNE1, KCNE2, KCNJ2), structural proteins (ANK2, GJA5, PALLD), sympathetic system modulators (ADRB1, ADRB2, ADRB3), blood pressure regulators (NOS1AP, PAI-1), modulators of ionic flows (PLN, CERKL, SLCO3A1), transcription factors (BRUNOL4, LITAF), regulators of cell morphology (NRG3) and other genes known to be associated to ECG intervals modulation (MDR1, CASQ2, NDRG4, NUBPL, RNF207; Supplementary Table S2).…”
Section: Genetic Analysismentioning
confidence: 99%