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Titel:

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

Dokumenttyp:
Journal Article; Article
Autor(en):
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.
Zeitschriftentitel:
Circulation
Jahr:
2017
Band / Volume:
135
Heft / Issue:
24
Seitenangaben Beitrag:
2336-2353
Sprache:
eng
Volltext / DOI:
doi:10.1161/CIRCULATIONAHA.116.022069
PubMed:
http://view.ncbi.nlm.nih.gov/pubmed/28461624
Print-ISSN:
0009-7322
TUM Einrichtung:
Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (Prof. Schunkert)
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