Loss of Cardioprotective Effects at theLocus as a Result of Gene-Smoking Interactions.

Saleheen, Danish; Zhao, Wei; Young, Robin; Nelson, Christopher P; Ho, WeangKee; Ferguson, Jane F; Rasheed, Asif; Ou, Kristy; Nurnberg, Sylvia T; Bauer, Robert C; Goel, Anuj; Do, Ron; Stewart, Alexandre F R; Hartiala, Jaana; Zhang, Weihua; Thorleifsson, Gudmar; Strawbridge, Rona J; Sinisalo, Juha; Kanoni, Stavroula; Sedaghat, Sanaz; Marouli, Eirini; Kristiansson, Kati; Hua Zhao, Jing; Scott, Robert; Gauguier, Dominique; Shah, Svati H; Smith, Albert Vernon; van Zuydam, Natalie; Cox, Amanda J; Willenborg, Christina; Kessler, Thorsten; Zeng, Lingyao; Province, Michael A; Ganna, Andrea; Lind, Lars; Pedersen, Nancy L; White, Charles C; Joensuu, Anni; Edi Kleber, Marcus; Hall, Alistair S; März, Winfried; Salomaa, Veikko; O'Donnell, Christopher; Ingelsson, Erik; Feitosa, Mary F; Erdmann, Jeanette; Bowden, Donald W; Palmer, Colin N A; Gudnason, Vilmundur; Faire, Ulf De; Zalloua, Pierre; Wareham, Nicholas; Thompson, John R; Kuulasmaa, Kari; Dedoussis, George; Perola, Markus; Dehghan, Abbas; Chambers, John C; Kooner, Jaspal; Allayee, Hooman; Deloukas, Panos; McPherson, Ruth; Stefansson, Kari; Schunkert, Heribert; Kathiresan, Sekar; Farrall, Martin; Marcel Frossard, Philippe; Rader, Daniel J; Samani, Nilesh J; Reilly, Muredach P

doi:10.1161/CIRCULATIONAHA.116.022069

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journal article

Title:: Loss of Cardioprotective Effects at theLocus as a Result of Gene-Smoking Interactions.
Document type:: Journal Article; Article
Author(s):: Saleheen, Danish; Zhao, Wei; Young, Robin; Nelson, Christopher P; Ho, WeangKee; Ferguson, Jane F; Rasheed, Asif; Ou, Kristy; Nurnberg, Sylvia T; Bauer, Robert C; Goel, Anuj; Do, Ron; Stewart, Alexandre F R; Hartiala, Jaana; Zhang, Weihua; Thorleifsson, Gudmar; Strawbridge, Rona J; Sinisalo, Juha; Kanoni, Stavroula; Sedaghat, Sanaz; Marouli, Eirini; Kristiansson, Kati; Hua Zhao, Jing; Scott, Robert; Gauguier, Dominique; Shah, Svati H; Smith, Albert Vernon; van Zuydam, Natalie; Cox, Amanda J; Willenborg, Christina; Kessler, Thorsten; Zeng, Lingyao; Province, Michael A; Ganna, Andrea; Lind, Lars; Pedersen, Nancy L; White, Charles C; Joensuu, Anni; Edi Kleber, Marcus; Hall, Alistair S; März, Winfried; Salomaa, Veikko; O'Donnell, Christopher; Ingelsson, Erik; Feitosa, Mary F; Erdmann, Jeanette; Bowden, Donald W; Palmer, Colin N A; Gudnason, Vilmundur; Faire, Ulf De; Zalloua, Pierre; Wareham, Nicholas; Thompson, John R; Kuulasmaa, Kari; Dedoussis, George; Perola, Markus; Dehghan, Abbas; Chambers, John C; Kooner, Jaspal; Allayee, Hooman; Deloukas, Panos; McPherson, Ruth; Stefansson, Kari; Schunkert, Heribert; Kathiresan, Sekar; Farrall, Martin; Marcel Frossard, Philippe; Rader, Daniel J; Samani, Nilesh J; Reilly, Muredach P «
Saleheen, Danish; Zhao, Wei; Young, Robin; Nelson, Christopher P; Ho, WeangKee; Ferguson, Jane F; Rasheed, Asif; Ou, Kristy; Nurnberg, Sylvia T; Bauer, Robert C; Goel, Anuj; Do, Ron; Stewart, Alexandre F R; Hartiala, Jaana; Zhang, Weihua; Thorleifsson, Gudmar; Strawbridge, Rona J; Sinisalo, Juha; Kanoni, Stavroula; Sedaghat, Sanaz; Marouli, Eirini; Kristiansson, Kati; Hua Zhao, Jing; Scott, Robert; Gauguier, Dominique; Shah, Svati H; Smith, Albert Vernon; van Zuydam, Natalie; Cox, Amanda J; Will... »
Abstract:: Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with genotypes that have been shown to associate with CHD risk.We analyzed data on 60 919 CHD cases and 80 243 controls from 29 studies for gene-smoking interactions for genetic variants at 45 loci previously reported to be associated with CHD risk. We also studied 5 loci associated with smoking behavior. Study-specific gene-smoking interaction effects were calculated and pooled using fixed-effects meta-analyses. Interaction analyses were declared to be significant at avalue of <1.0×10(Bonferroni correction for 50 tests).We identified novel gene-smoking interaction for a variant upstream of thegene. Every T allele of rs7178051 was associated with lower CHD risk by 12% in never-smokers (=1.3×10) in comparison with 5% in ever-smokers (=2.5×10), translating to a 60% loss of CHD protection conferred by this allelic variation in people who smoked tobacco (interactionvalue=8.7×10). The protective T allele at rs7178051 was also associated with reducedexpression in human aortic endothelial cells and lymphoblastoid cell lines. Exposure of human coronary artery smooth muscle cells to cigarette smoke extract led to induction ofCONCLUSIONS: Allelic variation at rs7178051 that associates with reducedexpression confers stronger CHD protection in never-smokers than in ever-smokers. Increased vascularexpression may contribute to the loss of CHD protection in smokers.
Journal title abbreviation:: Circulation
Year:: 2017
Journal volume:: 135
Journal issue:: 24
Pages contribution:: 2336-2353
Language:: eng
Fulltext / DOI:: doi:10.1161/CIRCULATIONAHA.116.022069
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/28461624
Print-ISSN:: 0009-7322
TUM Institution:: Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (Prof. Schunkert)
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Lehr- und Forschungskooperationen mit den Kliniken und Instituten am Deutschen Herzzentrum Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (DHM) (Prof. Schunkert)2017

mediaTUM Gesamtbestand Einrichtungen Hochschulpräsidium TUM Senior Excellence Faculty EoE Publikationen 2017