1 2
Department of Epidemiology and Department of Internal Medicine, Erasmus Medical Center, PO Box 2040, 3000 CA,
3
Rotterdam, The Netherlands, Center for Human Genetic Research, Cardiovascular Research Center, Massachusetts
4
General Hospital, Boston, MA 02114, USA, Dutch Medicines Evaluation Board, PO Box 16229, 2500 BE, The Hague,
5
The Netherlands, Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Ageing, Rotterdam,
6
The Netherlands and Inspectorate of Health Care, PO Box 16119, 2500 BC, The Hague, The Netherlands
Received June 4, 2009; Revised July 21, 2009; Accepted July 27, 2009本文来自优.文,论-文·网原文请找腾讯752018766
Common variation within the nitric oxide-1 synthase activator protein (NOS1AP) locus is strongly related to
QTinterval,asuddencardiacdeath(SCD)riskfactor.Arecentreportdescribescommonvariation inNOS1AP
associated with S
hindi sms http://www.hindisms-hindi.com/ CD in a US population of European ancestry. The objective of the current study was to
obtain additional evidence by investigating the association between NOS1AP variants and SCD in the pro-
spectivepopulation-basedRotterdamStudy. Thestudypopulation consisted of5974Europeanancestry sub-
jects, aged 55 years and older, genotyped on Illumina arrays. SCD was defined according to European
Society of Cardiology guidelines. Smoking, body mass index, diabetes mellitus, hypertension, heart failure
and myocardial infarction were used as covariates in Cox proportional hazard models. Results were com-
bined with reported evidence using inverse-variance weighted meta-analysis. Two hundred and eight (109
witnessed) cases of SCD occurred during a mean follow-up of 10.4 years. Within the Rotterdam Study
alone, no significant associations were observed. Upon pooling of results with existing data, we observed
strengthening of existing evidence for rs16847549 (US data HR 5 1.31, P 5 0.0024; Rotterdam Study HR 5
1.18, P 50.16; joint HR 51.26, P 5 0.0011). When the case definition in the Rotterdam Study was restricted
to witnessed SCD, association of rs16847549 with SCD became stronger (joint P5 0.00019) and additionally
the association between rs12567209 and SCD gained significance (US data HR 50.57, P5 0.0035; Rotterdam
Study HR 5 0.69, P 5 0.23; joint HR 5 0.60, P 5 0.0018). In conclusion, this study provided additional evi-
dence for association between genetic variation within NOS1AP and SCD. The mechanism by which this
effect is exerted remains to be elucidated.2494