OBJECTIVES: Genome wide association studies have consistently reported associations between a region on chromosome 9p21.3 and a broad range of vascular diseases, such as coronary artery disease (CAD), aortic and intracranial aneurysms and type-2 diabetes (T2D). However, clear associations with intermediate phenotypes have not been described so far. To shed light on a possible influence of this chromosomal region on arterial wall integrity, we analysed associations between single nucleotide polymorphisms (SNPs) and degree of stiffness of the abdominal aorta in elderly individuals. METHODS AND RESULTS: A total of 400 subjects, 212 men and 188 women, aged 70-88 years were included. Arterial stiffness was examined at the midpoint between the renal arteries and the aortic bifurcation. Two CAD- and aneurysm-associated SNPs (rs10757274 and rs2891168) and one T2D-associated SNP (rs1081161) within the 9p21.3 region were genotyped. Aortic compliance and distensibility coefficients were higher in carriers of the rs10757274G and rs2891168G alleles in men reflecting a decrease in aortic stiffness. Adjustment for age and mean arterial pressure had no effect on these associations. The two SNPs were not associated with intima-media thickness or lumen diameter of the abdominal aorta. There were no associations between the rs10811661 SNP and any measure of aortic stiffness. CONCLUSIONS: Impaired mechanical properties of the arterial wall may explain the association between chromosome 9p21.3 polymorphisms and vascular disease.
OBJECTIVES: Genome wide association studies have consistently reported associations between a region on chromosome 9p21.3 and a broad range of vascular diseases, such as coronary artery disease (CAD), aortic and intracranial aneurysms and type-2 diabetes (T2D). However, clear associations with intermediate phenotypes have not been described so far. To shed light on a possible influence of this chromosomal region on arterial wall integrity, we analysed associations between single nucleotide polymorphisms (SNPs) and degree of stiffness of the abdominal aorta in elderly individuals. METHODS AND RESULTS: A total of 400 subjects, 212 men and 188 women, aged 70-88 years were included. Arterial stiffness was examined at the midpoint between the renal arteries and the aortic bifurcation. Two CAD- and aneurysm-associated SNPs (rs10757274 and rs2891168) and one T2D-associated SNP (rs1081161) within the 9p21.3 region were genotyped. Aortic compliance and distensibility coefficients were higher in carriers of the rs10757274G and rs2891168G alleles in men reflecting a decrease in aortic stiffness. Adjustment for age and mean arterial pressure had no effect on these associations. The two SNPs were not associated with intima-media thickness or lumen diameter of the abdominal aorta. There were no associations between the rs10811661 SNP and any measure of aortic stiffness. CONCLUSIONS: Impaired mechanical properties of the arterial wall may explain the association between chromosome 9p21.3 polymorphisms and vascular disease.
Authors: Christopher J O'Donnell; Maryam Kavousi; Albert V Smith; Sharon L R Kardia; Mary F Feitosa; Shih-Jen Hwang; Yan V Sun; Michael A Province; Thor Aspelund; Abbas Dehghan; Udo Hoffmann; Lawrence F Bielak; Qunyuan Zhang; Gudny Eiriksdottir; Cornelia M van Duijn; Caroline S Fox; Mariza de Andrade; Aldi T Kraja; Sigurdur Sigurdsson; Suzette E Elias-Smale; Joanne M Murabito; Lenore J Launer; Aad van der Lugt; Sekar Kathiresan; Gabriel P Krestin; David M Herrington; Timothy D Howard; Yongmei Liu; Wendy Post; Braxton D Mitchell; Jeffrey R O'Connell; Haiqing Shen; Alan R Shuldiner; David Altshuler; Roberto Elosua; Veikko Salomaa; Stephen M Schwartz; David S Siscovick; Benjamin F Voight; Joshua C Bis; Nicole L Glazer; Bruce M Psaty; Eric Boerwinkle; Gerardo Heiss; Stefan Blankenberg; Tanja Zeller; Philipp S Wild; Renate B Schnabel; Arne Schillert; Andreas Ziegler; Thomas F Münzel; Charles C White; Jerome I Rotter; Michael Nalls; Matthijs Oudkerk; Andrew D Johnson; Anne B Newman; Andre G Uitterlinden; Joseph M Massaro; Julie Cunningham; Tamara B Harris; Albert Hofman; Patricia A Peyser; Ingrid B Borecki; L Adrienne Cupples; Vilmundur Gudnason; Jacqueline C M Witteman Journal: Circulation Date: 2011-12-05 Impact factor: 29.690
Authors: Scott G Prushik; Alik Farber; Philimon Gona; Peter Shrader; Michael J Pencina; Ralph B D'Agostino; Joanne M Murabito Journal: Am J Cardiol Date: 2011-12-10 Impact factor: 2.778
Authors: Aaron R Folsom; James S Pankow; Xiaohui Li; Daniel A Duprez; David R Jacobs; Ronald Klein; Barbara Klein; Weihong Tang; Tien Yin Wong; Mary Frances Cotch; Kent D Taylor; Stephen S Rich; Jennifer L Hall; Wendy S Post; Jerome I Rotter Journal: Atherosclerosis Date: 2013-08-02 Impact factor: 5.162