AIM: Since inflammation is an important contributor to atherosclerosis, gene variants mediating inflammation are of interest. We investigated gene variants in acute phase serum amyloid-A (SAA), a sensitive indicator of inflammatory activity, and their associations with cardiovascular disease (CVD) and HDL cholesterol. Interaction of the SAA genes with genetic variants of their regulators, IL-1, IL-6 and TNF-alpha in influencing CVD was also explored. METHODS: SNPs characterizing common variation in the SAA1 and SAA2 genes were genotyped in European-(EA) and African-American (AA) participants (n=3969 and n=719) of the Cardiovascular Health Study. Using linear and Cox proportional hazards regression, we assessed associations of SNPs with baseline carotid artery intima-media thickness (cIMT) and risk of incident myocardial infarction, ischemic stroke, total CVD events or mortality during 14 years of follow-up. RESULTS: No associations between SAA SNPs and outcomes were observed in EA, with the exception of total CVD events; each rs4638289 minor allele was associated with an increased risk in obese individuals, HR=1.2 (95%CI: 0.981.4; p=0.086) and decreased risk among non-obese, HR=0.9 (95%CI: 0.80.99; p=0.026). In AA, we observed modest associations between SAA SNPs and cIMT, potentially modified by HDL. SAA SNPs were also associated with lower HDL in EA and AA. Suggestive gene-gene interaction findings for cIMT in AA and CVD mortality in EA were not significant in subsequent model selection tests. CONCLUSION: Associations of SAA SNPs with cIMT, HDL and total CVD events were identified, unadjusted for multiple testing. These findings should be regarded as hypothesis-generating until confirmed by other studies.
AIM: Since inflammation is an important contributor to atherosclerosis, gene variants mediating inflammation are of interest. We investigated gene variants in acute phase serum amyloid-A (SAA), a sensitive indicator of inflammatory activity, and their associations with cardiovascular disease (CVD) and HDL cholesterol. Interaction of the SAA genes with genetic variants of their regulators, IL-1, IL-6 and TNF-alpha in influencing CVD was also explored. METHODS: SNPs characterizing common variation in the SAA1 and SAA2 genes were genotyped in European-(EA) and African-American (AA) participants (n=3969 and n=719) of the Cardiovascular Health Study. Using linear and Cox proportional hazards regression, we assessed associations of SNPs with baseline carotid artery intima-media thickness (cIMT) and risk of incident myocardial infarction, ischemic stroke, total CVD events or mortality during 14 years of follow-up. RESULTS: No associations between SAA SNPs and outcomes were observed in EA, with the exception of total CVD events; each rs4638289 minor allele was associated with an increased risk in obese individuals, HR=1.2 (95%CI: 0.981.4; p=0.086) and decreased risk among non-obese, HR=0.9 (95%CI: 0.80.99; p=0.026). In AA, we observed modest associations between SAA SNPs and cIMT, potentially modified by HDL. SAA SNPs were also associated with lower HDL in EA and AA. Suggestive gene-gene interaction findings for cIMT in AA and CVD mortality in EA were not significant in subsequent model selection tests. CONCLUSION: Associations of SAA SNPs with cIMT, HDL and total CVD events were identified, unadjusted for multiple testing. These findings should be regarded as hypothesis-generating until confirmed by other studies.
Authors: Alexander P Reiner; Elad Ziv; Denise L Lind; Caroline M Nievergelt; Nicholas J Schork; Steven R Cummings; Angie Phong; Esteban González Burchard; Tamara B Harris; Bruce M Psaty; Pui-Yan Kwok Journal: Am J Hum Genet Date: 2005-01-19 Impact factor: 11.025
Authors: Martin Schillinger; Markus Exner; Wolfgang Mlekusch; Schila Sabeti; Jasmin Amighi; Robert Nikowitsch; Ewald Timmel; Bernhard Kickinger; Christoph Minar; Matthias Pones; Wolfgang Lalouschek; Helmut Rumpold; Gerald Maurer; Oswald Wagner; Erich Minar Journal: Circulation Date: 2005-04-25 Impact factor: 29.690
Authors: Anisa Jahangiri; Maria C de Beer; Victoria Noffsinger; Lisa R Tannock; Chandrashekar Ramaiah; Nancy R Webb; Deneys R van der Westhuyzen; Frederick C de Beer Journal: Arterioscler Thromb Vasc Biol Date: 2008-11-13 Impact factor: 8.311
Authors: Anna-Isabelle Kälsch; Hubert Scharnagl; Marcus E Kleber; Christian Windpassinger; Wolfgang Sattler; Jan Leipe; Bernhard K Krämer; Winfried März; Ernst Malle Journal: Clin Res Cardiol Date: 2019-07-01 Impact factor: 5.460