OBJECTIVES: The chromosomal loci 9p21.3, 6q25.1, and 2q36.3, represented by their respective leading variants rs1333049, rs6922269 and rs2943634, have been linked with a history of coronary artery disease (CAD) by genome-wide association studies. Whereas the association of variant rs1333049 with CAD was analysed in several subsequent studies, replication studies of variants rs6922269 and rs2943634 are missing. Furthermore, no direct association with coronary atherosclerosis has been established. We therefore aimed at investigating the association of the above variants with coronary atherosclerosis. METHODS: We performed genotyping in two large cohorts of consecutive Caucasian patients undergoing coronary angiography for the evaluation of suspected or established stable CAD, comprising 671 and 940 patients, respectively, with a total of 1611 subjects. RESULTS: In models of dominant inheritance, variant rs1333049 conferred a significantly increased risk of significant coronary stenoses with lumen narrowing >or=50% in both study cohorts, with adjusted odd ratios (OR) of 1.71 (1.15-2.52); p=0.007 and 1.55 (1.10-2.18); p=0.012, respectively. Variant rs6922269 in neither cohort was significantly associated with CAD. Although carriers of the A allele of variant rs2943634 were at an increased risk of significant coronary stenoses in the second cohort (OR=1.41 (1.06-1.88); p=0.018), no such association was found for the first cohort nor for both cohorts combined. CONCLUSION: Our data from two populations show that variant rs1333049 is significantly associated with angiographically characterized CAD. In contrast, variant rs6922269 did not show any impact on coronary atherosclerosis. The association between variant rs2943634 and CAD warrants further investigation.
OBJECTIVES: The chromosomal loci 9p21.3, 6q25.1, and 2q36.3, represented by their respective leading variants rs1333049, rs6922269 and rs2943634, have been linked with a history of coronary artery disease (CAD) by genome-wide association studies. Whereas the association of variant rs1333049 with CAD was analysed in several subsequent studies, replication studies of variants rs6922269 and rs2943634 are missing. Furthermore, no direct association with coronary atherosclerosis has been established. We therefore aimed at investigating the association of the above variants with coronary atherosclerosis. METHODS: We performed genotyping in two large cohorts of consecutive Caucasian patients undergoing coronary angiography for the evaluation of suspected or established stable CAD, comprising 671 and 940 patients, respectively, with a total of 1611 subjects. RESULTS: In models of dominant inheritance, variant rs1333049 conferred a significantly increased risk of significant coronary stenoses with lumen narrowing >or=50% in both study cohorts, with adjusted odd ratios (OR) of 1.71 (1.15-2.52); p=0.007 and 1.55 (1.10-2.18); p=0.012, respectively. Variant rs6922269 in neither cohort was significantly associated with CAD. Although carriers of the A allele of variant rs2943634 were at an increased risk of significant coronary stenoses in the second cohort (OR=1.41 (1.06-1.88); p=0.018), no such association was found for the first cohort nor for both cohorts combined. CONCLUSION: Our data from two populations show that variant rs1333049 is significantly associated with angiographically characterized CAD. In contrast, variant rs6922269 did not show any impact on coronary atherosclerosis. The association between variant rs2943634 and CAD warrants further investigation.
Authors: J A Hubacek; V Staněk; M Gebauerová; R Poledne; M Aschermann; H Skalická; J Matoušková; A Kruger; M Pěnička; H Hrabáková; J Veselka; P Hájek; V Lánská; V Adámková; J Pitˇha Journal: Mol Biol Rep Date: 2015-03-26 Impact factor: 2.316
Authors: Thomas M Morgan; John A House; Sharon Cresci; Philip Jones; Hooman Allayee; Stanley L Hazen; Yesha Patel; Riyaz S Patel; Danny J Eapen; Salina P Waddy; Arshed A Quyyumi; Marcus E Kleber; Winfried März; Bernhard R Winkelmann; Bernhard O Boehm; Harlan M Krumholz; John A Spertus Journal: BMC Med Genet Date: 2011-09-29 Impact factor: 2.103
Authors: Kenneth Chan; Riyaz S Patel; Paul Newcombe; Christopher P Nelson; Atif Qasim; Stephen E Epstein; Susan Burnett; Viola L Vaccarino; A Maziar Zafari; Svati H Shah; Jeffrey L Anderson; John F Carlquist; Jaana Hartiala; Hooman Allayee; Kunihiko Hinohara; Bok-Soo Lee; Anna Erl; Katrina L Ellis; Anuj Goel; Arne S Schaefer; Nour Eddine El Mokhtari; Benjamin A Goldstein; Mark A Hlatky; Alan S Go; Gong-Qing Shen; Yan Gong; Carl Pepine; Ross C Laxton; John C Whittaker; W H Wilson Tang; Julie A Johnson; Qing K Wang; Themistocles L Assimes; Ute Nöthlings; Martin Farrall; Hugh Watkins; A Mark Richards; Vicky A Cameron; Axel Muendlein; Heinz Drexel; Werner Koch; Jeong Euy Park; Akinori Kimura; Wei-feng Shen; Iain A Simpson; Stanley L Hazen; Benjamin D Horne; Elizabeth R Hauser; Arshed A Quyyumi; Muredach P Reilly; Nilesh J Samani; Shu Ye Journal: J Am Coll Cardiol Date: 2013-01-23 Impact factor: 24.094