AIM: Recently, a polymorphism in the NOS1AP gene (rs10494366), a regulator of neuronal nitric oxide synthase (nNOS), was associated with QTc prolongation. Both nNOS and calcium channel blockers (CCBs) regulate intracellular calcium levels and have an important role in cardiovascular homeostasis. The aim was to investigate whether this polymorphism is associated with cardiovascular mortality in users of CCBs. METHODS: The data from the Rotterdam study, a population-based closed cohort study of Caucasian individuals of > or =55 years of age, were used. We identified 1113 participants in the Rotterdam Study who were prescribed CCBs for the first time between 1991 and 2005. All-cause and cardiovascular mortality was assessed in participants who were prescribed CCBs with different NOS1AP rs10494366 genotypes using Cox proportional hazard models. RESULTS: In participants starting on dihydropyridine CCBs (amlodipine, nifedipine and others) all-cause mortality (n = 79) risks were higher in participants with the TG [hazard ratio (HR) 2.57, 95% confidence interval (CI) 1.24, 5.34] or the GG genotype (HR 3.18, 95% CI 1.18, 8.58) than in participants with the referent TT genotype. Cardiovascular mortality (n = 54) risks were 3.51 (95% CI 1.41, 8.78) for the TG genotype and 6.00 (95% CI 1.80, 20.0) for the GG genotype. No differences in all-cause mortality or cardiovascular mortality were seen in participants starting with the nondihydropyridine CCBs verapamil or diltiazem. CONCLUSION: The minor G allele of rs10494366 in the NOS1AP gene is associated with increased all-cause and cardiovascular mortality in Caucasian users of dihydropyridine CCBs. The mechanism underlying the observed association is unknown.
AIM: Recently, a polymorphism in the NOS1AP gene (rs10494366), a regulator of neuronal nitric oxide synthase (nNOS), was associated with QTc prolongation. Both nNOS and calcium channel blockers (CCBs) regulate intracellular calcium levels and have an important role in cardiovascular homeostasis. The aim was to investigate whether this polymorphism is associated with cardiovascular mortality in users of CCBs. METHODS: The data from the Rotterdam study, a population-based closed cohort study of Caucasian individuals of > or =55 years of age, were used. We identified 1113 participants in the Rotterdam Study who were prescribed CCBs for the first time between 1991 and 2005. All-cause and cardiovascular mortality was assessed in participants who were prescribed CCBs with different NOS1APrs10494366 genotypes using Cox proportional hazard models. RESULTS: In participants starting on dihydropyridine CCBs (amlodipine, nifedipine and others) all-cause mortality (n = 79) risks were higher in participants with the TG [hazard ratio (HR) 2.57, 95% confidence interval (CI) 1.24, 5.34] or the GG genotype (HR 3.18, 95% CI 1.18, 8.58) than in participants with the referent TT genotype. Cardiovascular mortality (n = 54) risks were 3.51 (95% CI 1.41, 8.78) for the TG genotype and 6.00 (95% CI 1.80, 20.0) for the GG genotype. No differences in all-cause mortality or cardiovascular mortality were seen in participants starting with the nondihydropyridine CCBsverapamil or diltiazem. CONCLUSION: The minor G allele of rs10494366 in the NOS1AP gene is associated with increased all-cause and cardiovascular mortality in Caucasian users of dihydropyridine CCBs. The mechanism underlying the observed association is unknown.
Authors: Claire E Sears; Simon M Bryant; Euan A Ashley; Craig A Lygate; Stevan Rakovic; Helen L Wallis; Stefan Neubauer; Derek A Terrar; B Casadei Journal: Circ Res Date: 2003-03-06 Impact factor: 17.367
Authors: M Dittrich; J Jurevicius; M Georget; F Rochais; B Fleischmann; J Hescheler; R Fischmeister Journal: J Physiol Date: 2001-07-01 Impact factor: 5.182
Authors: Dan E Arking; Arne Pfeufer; Wendy Post; W H Linda Kao; Christopher Newton-Cheh; Morna Ikeda; Kristen West; Carl Kashuk; Mahmut Akyol; Siegfried Perz; Shapour Jalilzadeh; Thomas Illig; Christian Gieger; Chao-Yu Guo; Martin G Larson; H Erich Wichmann; Eduardo Marbán; Christopher J O'Donnell; Joel N Hirschhorn; Stefan Kääb; Peter M Spooner; Thomas Meitinger; Aravinda Chakravarti Journal: Nat Genet Date: 2006-04-30 Impact factor: 38.330
Authors: Natalie Burkard; Adam G Rokita; Susann G Kaufmann; Matthias Hallhuber; Rongxue Wu; Kai Hu; Ulrich Hofmann; Andreas Bonz; Stefan Frantz; Elizabeth J Cartwright; Ludwig Neyses; Lars S Maier; Sebastian K G Maier; Thomas Renné; Kai Schuh; Oliver Ritter Journal: Circ Res Date: 2007-02-01 Impact factor: 17.367
Authors: Fabrizio De Ponti; Elisabetta Poluzzi; Andrea Cavalli; Maurizio Recanatini; Nicola Montanaro Journal: Drug Saf Date: 2002 Impact factor: 5.606
Authors: Wendy Post; Haiqing Shen; Coleen Damcott; Dan E Arking; W H Linda Kao; Paul A Sack; Kathleen A Ryan; Aravinda Chakravarti; Braxton D Mitchell; Alan R Shuldiner Journal: Hum Hered Date: 2007-06-12 Impact factor: 0.444
Authors: Matthijs L Becker; Albert-Jan L H J Aarnoudse; Christopher Newton-Cheh; Albert Hofman; Jacqueline C M Witteman; André G Uitterlinden; Loes E Visser; Bruno H Ch Stricker Journal: Pharmacogenet Genomics Date: 2008-07 Impact factor: 2.089
Authors: Albert Hofman; Monique M B Breteler; Cornelia M van Duijn; Gabriel P Krestin; Huibert A Pols; Bruno H Ch Stricker; Henning Tiemeier; André G Uitterlinden; Johannes R Vingerling; Jacqueline C M Witteman Journal: Eur J Epidemiol Date: 2007-10-23 Impact factor: 8.082
Authors: Glenn I Fishman; Sumeet S Chugh; John P Dimarco; Christine M Albert; Mark E Anderson; Robert O Bonow; Alfred E Buxton; Peng-Sheng Chen; Mark Estes; Xavier Jouven; Raymond Kwong; David A Lathrop; Alice M Mascette; Jeanne M Nerbonne; Brian O'Rourke; Richard L Page; Dan M Roden; David S Rosenbaum; Nona Sotoodehnia; Natalia A Trayanova; Zhi-Jie Zheng Journal: Circulation Date: 2010-11-30 Impact factor: 29.690
Authors: Lia Crotti; Maria Cristina Monti; Roberto Insolia; Anna Peljto; Althea Goosen; Paul A Brink; David A Greenberg; Peter J Schwartz; Alfred L George Journal: Circulation Date: 2009-10-12 Impact factor: 29.690
Authors: Daniel R Gonzalez; Adriana Treuer; Qi-An Sun; Jonathan S Stamler; Joshua M Hare Journal: J Cardiovasc Pharmacol Date: 2009-09 Impact factor: 3.105
Authors: Dan M Roden; Julie A Johnson; Stephen E Kimmel; Ronald M Krauss; Marisa Wong Medina; Alan Shuldiner; Russell A Wilke Journal: Circ Res Date: 2011-09-16 Impact factor: 17.367
Authors: Ilja M Nolte; Chris Wallace; Stephen J Newhouse; Daryl Waggott; Jingyuan Fu; Nicole Soranzo; Rhian Gwilliam; Panos Deloukas; Irina Savelieva; Dongling Zheng; Chrysoula Dalageorgou; Martin Farrall; Nilesh J Samani; John Connell; Morris Brown; Anna Dominiczak; Mark Lathrop; Eleftheria Zeggini; Louise V Wain; Christopher Newton-Cheh; Mark Eijgelsheim; Kenneth Rice; Paul I W de Bakker; Arne Pfeufer; Serena Sanna; Dan E Arking; Folkert W Asselbergs; Tim D Spector; Nicholas D Carter; Steve Jeffery; Martin Tobin; Mark Caulfield; Harold Snieder; Andrew D Paterson; Patricia B Munroe; Yalda Jamshidi Journal: PLoS One Date: 2009-07-09 Impact factor: 3.240