BACKGROUND: Apolipoprotein E gene (APOE) interacts with environmental factors in defining risk for atherosclerosis. We studied whether the APOE epsilon2/epsilon3/epsilon4 genotype or APOE promoter polymorphisms -219G/T and +113G/C might interact with smoking on the development of fatty streaks. We also studied the previously unknown effects of +113G/C on transcriptional activity. METHODS AND RESULTS: The fatty streak areas of aorta were measured morphometrically in subjects of the Helsinki Sudden Death Study. Within APOE epsilon3/epsilon3 subjects, there was a strong interaction between smoking and both -219G/T (P=0.009) and +113G/C (P=0.003) promoter polymorphisms on abdominal aorta fatty streak area: the -219T- and +113C-allele carriers had larger lesion areas compared with G/G (12.7% versus 5.9%, P=0.007; 12.9% versus 6.3%, P=0.010, respectively) within nonsmokers. Within smokers, the associations were inverse. Moreover, smoking increased the fatty streak area within -219G/G or +113G/G genotypes and -219G/+113G/epsilon3 haplotype carriers. Functional studies in reporter assay showed that in comparison with the +113G allele, the +113C allele had higher transcriptional activity and bound transcription factors from liver cell nuclear extract with significantly lower affinity. CONCLUSIONS: In middle-aged Finnish men with APOE epsilon3/epsilon3 genotype, the APOE promoter polymorphisms -219G/T and +113G/C interact with smoking in modulating aortic atherosclerosis. The +113G/C polymorphism has an effect on transcriptional activity.
BACKGROUND:Apolipoprotein E gene (APOE) interacts with environmental factors in defining risk for atherosclerosis. We studied whether the APOE epsilon2/epsilon3/epsilon4 genotype or APOE promoter polymorphisms -219G/T and +113G/C might interact with smoking on the development of fatty streaks. We also studied the previously unknown effects of +113G/C on transcriptional activity. METHODS AND RESULTS: The fatty streak areas of aorta were measured morphometrically in subjects of the Helsinki Sudden Death Study. Within APOE epsilon3/epsilon3 subjects, there was a strong interaction between smoking and both -219G/T (P=0.009) and +113G/C (P=0.003) promoter polymorphisms on abdominal aorta fatty streak area: the -219T- and +113C-allele carriers had larger lesion areas compared with G/G (12.7% versus 5.9%, P=0.007; 12.9% versus 6.3%, P=0.010, respectively) within nonsmokers. Within smokers, the associations were inverse. Moreover, smoking increased the fatty streak area within -219G/G or +113G/G genotypes and -219G/+113G/epsilon3 haplotype carriers. Functional studies in reporter assay showed that in comparison with the +113G allele, the +113C allele had higher transcriptional activity and bound transcription factors from liver cell nuclear extract with significantly lower affinity. CONCLUSIONS: In middle-aged Finnish men with APOE epsilon3/epsilon3 genotype, the APOE promoter polymorphisms -219G/T and +113G/C interact with smoking in modulating aortic atherosclerosis. The +113G/C polymorphism has an effect on transcriptional activity.
Authors: Joanne M Murabito; Charles C White; Maryam Kavousi; Yan V Sun; Mary F Feitosa; Vijay Nambi; Claudia Lamina; Arne Schillert; Stefan Coassin; Joshua C Bis; Linda Broer; Dana C Crawford; Nora Franceschini; Ruth Frikke-Schmidt; Margot Haun; Suzanne Holewijn; Jennifer E Huffman; Shih-Jen Hwang; Stefan Kiechl; Barbara Kollerits; May E Montasser; Ilja M Nolte; Megan E Rudock; Andrea Senft; Alexander Teumer; Pim van der Harst; Veronique Vitart; Lindsay L Waite; Andrew R Wood; Christina L Wassel; Devin M Absher; Matthew A Allison; Najaf Amin; Alice Arnold; Folkert W Asselbergs; Yurii Aulchenko; Stefania Bandinelli; Maja Barbalic; Mladen Boban; Kristin Brown-Gentry; David J Couper; Michael H Criqui; Abbas Dehghan; Martin den Heijer; Benjamin Dieplinger; Jingzhong Ding; Marcus Dörr; Christine Espinola-Klein; Stephan B Felix; Luigi Ferrucci; Aaron R Folsom; Gustav Fraedrich; Quince Gibson; Robert Goodloe; Grgo Gunjaca; Meinhard Haltmayer; Gerardo Heiss; Albert Hofman; Arne Kieback; Lambertus A Kiemeney; Ivana Kolcic; Iftikhar J Kullo; Stephen B Kritchevsky; Karl J Lackner; Xiaohui Li; Wolfgang Lieb; Kurt Lohman; Christa Meisinger; David Melzer; Emile R Mohler; Ivana Mudnic; Thomas Mueller; Gerjan Navis; Friedrich Oberhollenzer; Jeffrey W Olin; Jeff O'Connell; Christopher J O'Donnell; Walter Palmas; Brenda W Penninx; Astrid Petersmann; Ozren Polasek; Bruce M Psaty; Barbara Rantner; Ken Rice; Fernando Rivadeneira; Jerome I Rotter; Adrie Seldenrijk; Marietta Stadler; Monika Summerer; Toshiko Tanaka; Anne Tybjaerg-Hansen; Andre G Uitterlinden; Wiek H van Gilst; Sita H Vermeulen; Sarah H Wild; Philipp S Wild; Johann Willeit; Tanja Zeller; Tatijana Zemunik; Lina Zgaga; Themistocles L Assimes; Stefan Blankenberg; Eric Boerwinkle; Harry Campbell; John P Cooke; Jacqueline de Graaf; David Herrington; Sharon L R Kardia; Braxton D Mitchell; Anna Murray; Thomas Münzel; Anne B Newman; Ben A Oostra; Igor Rudan; Alan R Shuldiner; Harold Snieder; Cornelia M van Duijn; Uwe Völker; Alan F Wright; H-Erich Wichmann; James F Wilson; Jacqueline C M Witteman; Yongmei Liu; Caroline Hayward; Ingrid B Borecki; Andreas Ziegler; Kari E North; L Adrienne Cupples; Florian Kronenberg Journal: Circ Cardiovasc Genet Date: 2011-12-23
Authors: Israa M Shatwan; Michelle Weech; Kim G Jackson; Julie A Lovegrove; Karani S Vimaleswaran Journal: Lipids Health Dis Date: 2017-11-23 Impact factor: 3.876
Authors: Israa M Shatwan; Kristian Hillert Winther; Basma Ellahi; Peter Elwood; Yoav Ben-Shlomo; Ian Givens; Margaret P Rayman; Julie A Lovegrove; Karani S Vimaleswaran Journal: Lipids Health Dis Date: 2018-04-30 Impact factor: 3.876