title: A Variant in COX-2 Gene Is Associated with Left Main Coronary Artery Disease and Clinical Outcomes of Coronary Artery Bypass Grafting.
abstract: As a particular severe phenotype of coronary artery disease (CAD), left main coronary artery disease (LMCAD) is heritable. Genetic variants related to prostaglandin metabolism are associated with LMCAD. Cyclooxygenase-2 (COX-2), a key synthase in prostaglandin pathways, displays high density in atherosclerotic lesions and promotes early atherosclerosis in CAD progression. We hypothesized that genetic variants in COX-2 gene contribute to LMCAD phenotype susceptibility compared to more peripheral coronary artery disease (MPCAD). In this study, we genotyped COX-2 rs5275, rs5277, and rs689466 of 1544 CAD patients undergoing coronary artery bypass grafting (CABG) and found that rs5277 C allele carriage was associated with LMCAD (adjusted OR: 1.590; 95% CI: 1.103~2.291;p= 0.013). Furtherly, long-term follow-up data suggested that rs5277 C allele carriage increased risk of major adverse cardiac and cerebrovascular events (MACCE) in the whole cohort (adjusted HR: 1.561; 95% CI: 1.025~2.377;p= 0.038) and LMCAD subgroup (adjusted HR: 2.014; 95% CI: 1.036~3.913;p= 0.039) but not in MPCAD subgroup (adjusted HR: 1.375; 95% CI: 0.791~2.392;p= 0.259). In conclusion, we demonstrate that COX-2 rs5277 C allele increases the risk of left main coronary artery lesion and is also correlated with poor prognosis of LMCAD patients with CABG therapy.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Hanning
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhengxi
authors.identifier: 0000-0002-8540-9061
authors.initials: Z
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Dachuan
authors.identifier: 0000-0001-5773-5540
authors.initials: D
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiao
authors.identifier: 0000-0002-1479-5049
authors.initials: X
authors.lastname: Teng
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yan
authors.identifier: 0000-0002-4773-1391
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhe
authors.identifier: 0000-0002-9162-6492
authors.initials: Z
authors.lastname: Zheng
mesh_terms: D000368:Aged; D000483:Alleles; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000601:surgery; D051546:Cyclooxygenase 2 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human