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Genetic variations in nitric oxide synthase 1 adaptor protein are associated with sudden cardiac death in US white community-based populations.
Tuesday,2012-11-06 12:10 America/Los_Angeles — eenright
| Title | Genetic variations in nitric oxide synthase 1 adaptor protein are associated with sudden cardiac death in US white community-based populations. |
| Publication Type | Journal Article |
| Year of Publication | 2009 |
| Authors | Kao, LWH, Arking, DE, Post, W, Rea, TD, Sotoodehnia, N, Prineas, RJ, Bishe, B, Doan, BQ, Boerwinkle, E, Psaty, BM, Tomaselli, GF, Coresh, J, Siscovick, DS, Marbán, E, Spooner, PM, Burke, GL, Chakravarti, A |
| Journal | Circulation |
| Volume | 119 |
| Issue | 7 |
| Pagination | 940-51 |
| Date Published | 2009 Feb 24 |
| ISSN | 1524-4539 |
| Keywords | Adaptor Proteins, Signal Transducing, Aged, Death, Sudden, Cardiac, Electrocardiography, European Continental Ancestry Group, Genotype, Humans, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors |
| Abstract | <p><b>BACKGROUND: </b>The ECG QT interval is associated with risk of sudden cardiac death (SCD). A previous genome-wide association study demonstrated that allelic variants (rs10494366 and rs4657139) in the nitric oxide synthase 1 adaptor protein (NOS1AP), which encodes a carboxy-terminal PDZ ligand of neuronal nitric oxide synthase, are associated with the QT interval in white adults. The present analysis was conducted to validate the association between NOS1AP variants and the QT interval and to examine the association with SCD in a combined population of 19 295 black and white adults from the Atherosclerosis Risk In Communities Study and the Cardiovascular Health Study.</p><p><b>METHODS AND RESULTS: </b>We examined 19 tagging single-nucleotide polymorphisms in the genomic blocks containing rs10494366 and rs4657139 in NOS1AP. SCD was defined as a sudden pulseless condition of cardiac origin in a previously stable individual. General linear models and Cox proportional hazards regression models were used. Multiple single-nucleotide polymorphisms in NOS1AP, including rs10494366, rs4657139, and rs16847548, were significantly associated with adjusted QT interval in whites (P<0.0001). In whites, after adjustment for age, sex, and study, the relative hazard of SCD associated with each C allele at rs16847548 was 1.31 (95% confidence interval 1.10 to 1.56, P=0.002), assuming an additive model. In addition, a downstream neighboring single-nucleotide polymorphism, rs12567209, which was not correlated with rs16847548 or QT interval, was also independently associated with SCD in whites (relative hazard 0.57, 95% confidence interval 0.39 to 0.83, P=0.003). Adjustment for QT interval and coronary heart disease risk factors attenuated but did not eliminate the association between rs16847548 and SCD, and such adjustment had no effect on the association between rs12567209 and SCD. No significant associations between tagging single-nucleotide polymorphisms in NOS1AP and either QT interval or SCD were observed in blacks.</p><p><b>CONCLUSIONS: </b>In a combined analysis of 2 population-based prospective cohort studies, sequence variations in NOS1AP were associated with baseline QT interval and the risk of SCD in white US adults.</p> |
| DOI | 10.1161/CIRCULATIONAHA.108.791723 |
| Alternate Journal | Circulation |
| PubMed ID | 19204306 |
| PubMed Central ID | PMC2782762 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States N01 HC 85085 / HC / NHLBI NIH HHS / United States N01 HC 85083 / HC / NHLBI NIH HHS / United States K01 DK067207 / DK / NIDDK NIH HHS / United States N01 HC 55018 / HC / NHLBI NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States U01 HL 080295 / HL / NHLBI NIH HHS / United States N01 HC 55021 / HC / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01 HC 75150 / HC / NHLBI NIH HHS / United States U54 HG002757 / HG / NHGRI NIH HHS / United States K01 DK 067207 / DK / NIDDK NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01 HC 85084 / HC / NHLBI NIH HHS / United States N01 HC 85086 / HC / NHLBI NIH HHS / United States N01 HC 35129 / HC / NHLBI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01 HC 85081 / HC / NHLBI NIH HHS / United States N01 HC 85079 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States HG 02757 / HG / NHGRI NIH HHS / United States N01 HC 55022 / HC / NHLBI NIH HHS / United States N01 HC 55019 / HC / NHLBI NIH HHS / United States U54 HG002757-01 / HG / NHGRI NIH HHS / United States N01 HC 55222 / HC / NHLBI NIH HHS / United States N01 HC 55016 / HC / NHLBI NIH HHS / United States N01 HC 45133 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States N01 HC 85080 / HC / NHLBI NIH HHS / United States N01 HC 55015 / HC / NHLBI NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01 HC 15103 / HC / NHLBI NIH HHS / United States U54 HG002757-02 / HG / NHGRI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC 85082 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC 55020 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States |