BACKGROUND: Thrombomodulin is an anticoagulant expressed during endothelial activation and damage. To address the potential role of allelic variants of thrombomodulin gene in the pathogenesis of cardiovascular diseases, we analyzed in a prospective follow-up study 8 single-nucleotide polymorphisms (SNPs) across the thrombomodulin locus, covering all common (>5%) haplotypes. METHODS AND RESULTS: Two separate, stratified random samples of men and women 25 to 74 years of age were examined in Finland in 1992 and 1997. The total sample size was 14 140 individuals, with 7 (1997 cohort) to 10 (1992 cohort) years of follow-up. Altogether, 662 individuals had a history of cardiovascular events already at baseline. During the follow-up, 401 incident coronary events and 148 incident ischemic strokes were observed. The alleles and common haplotypes of 8 SNPs were tested in Cox proportional hazards models using incident coronary events, incident ischemic strokes, and total mortality as end points. None of the SNPs or major SNP haplotypes showed consistent association with the end points analyzed in the combined data. CONCLUSIONS: Results from this prospective, population-based study suggest that common allelic variants of the thrombomodulin gene may not significantly contribute to the risk of cardiovascular events at the population level.
BACKGROUND:Thrombomodulin is an anticoagulant expressed during endothelial activation and damage. To address the potential role of allelic variants of thrombomodulin gene in the pathogenesis of cardiovascular diseases, we analyzed in a prospective follow-up study 8 single-nucleotide polymorphisms (SNPs) across the thrombomodulin locus, covering all common (>5%) haplotypes. METHODS AND RESULTS: Two separate, stratified random samples of men and women 25 to 74 years of age were examined in Finland in 1992 and 1997. The total sample size was 14 140 individuals, with 7 (1997 cohort) to 10 (1992 cohort) years of follow-up. Altogether, 662 individuals had a history of cardiovascular events already at baseline. During the follow-up, 401 incident coronary events and 148 incident ischemic strokes were observed. The alleles and common haplotypes of 8 SNPs were tested in Cox proportional hazards models using incident coronary events, incident ischemic strokes, and total mortality as end points. None of the SNPs or major SNP haplotypes showed consistent association with the end points analyzed in the combined data. CONCLUSIONS: Results from this prospective, population-based study suggest that common allelic variants of the thrombomodulin gene may not significantly contribute to the risk of cardiovascular events at the population level.
Authors: Thomas J Raife; Denis M Dwyre; Jeff W Stevens; Rochelle A Erger; Lorie Leo; Katina M Wilson; Jose A Fernández; Jennifer Wilder; Hyung-Suk Kim; John H Griffin; Nobuyo Maeda; Steven R Lentz Journal: Arterioscler Thromb Vasc Biol Date: 2011-11 Impact factor: 8.311
Authors: Joshua W Knowles; Huijan Wang; Haruka Itakura; Audrey Southwick; Richard M Myers; Carlos Iribarren; Stephen P Fortmann; Alan S Go; Thomas Quertermous; Mark A Hlatky Journal: Am Heart J Date: 2007-12 Impact factor: 4.749
Authors: Mervi Alanne; Kati Kristiansson; Kirsi Auro; Kaisa Silander; Kari Kuulasmaa; Leena Peltonen; Veikko Salomaa; Markus Perola Journal: Hum Genet Date: 2007-07-20 Impact factor: 4.132
Authors: Kirsi Auro; Mervi Alanne; Kati Kristiansson; Kaisa Silander; Kari Kuulasmaa; Veikko Salomaa; Leena Peltonen; Markus Perola Journal: PLoS Genet Date: 2007-06-07 Impact factor: 5.917
Authors: Kaisa Silander; Mervi Alanne; Kati Kristiansson; Olli Saarela; Samuli Ripatti; Kirsi Auro; Juha Karvanen; Sangita Kulathinal; Matti Niemelä; Pekka Ellonen; Erkki Vartiainen; Pekka Jousilahti; Janna Saarela; Kari Kuulasmaa; Alun Evans; Markus Perola; Veikko Salomaa; Leena Peltonen Journal: PLoS One Date: 2008-10-31 Impact factor: 3.240