Abstract
Selenoprotein S (SEPS1) is a novel candidate gene involved in the regulation of inflammatory response and protection from oxidative damage. This study explored the genetic variation in the SEPS1 locus for an association with CVD as well as with quantitative phenotypes related to obesity and inflammation. We used the case-cohort design and time-to-event analysis in two separate prospectively followed population-based cohorts FINRISK 92 and 97 (n = 999 and 1,223 individuals, respectively) to study the associations of five single nucleotide polymorphisms with the risk for coronary heart disease (CHD) and ischemic stroke events. We found a significant association with increased CHD risk in females carrying the minor allele of rs8025174 in the combined analysis of both cohorts [hazard ratio (HR) 2.95 (95% confidence interval: 1.37–6.39)]. Another variant, rs7178239, increased the risk for ischemic stroke significantly in females [HR: 3.35 (1.66–6.76)] and in joint analysis of both sexes and both cohorts [HR: 1.75 (1.17–2.64)]. These results indicate that variation in the SEPS1 locus may have an effect on CVD morbidity, especially in females. This observation should stimulate further investigations of the role of this gene and protein in the pathogenesis of CVD.
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Acknowledgments
We thank all participants of the FINRISK 92 and 97 studies. KTL Analytical Biochemistry laboratory is acknowledged for the laboratory measurements. Mrs. Anne Nyberg, Mrs. Siv Knaapila and Mrs. Minna Suvela are thanked for their skillful contribution in the genotyping process. Mrs. Siv Knaapila and MSc. Minttu Jussila are thanked for their participation in the DNA aliquotting process. MORGAM Data Centre is thanked for data management and assistance in the analysis procedures. We greatly appreciate the help from Dr. Joanne Curran during TagMan genotyping and at planning stage of the project. This study was supported by the Research Foundation of Orion Corporation, the Finnish Foundation for Cardiovascular Research, Aarne Koskelo Foundation, Jenny and Antti Wihuri Foundation and Sigrid Juselius Foundation. This study is a part of the GenomEUtwin—project (http://www.genomeutwin.org), which is supported by the European Commission under the programme “Quality of Life and Management of the Living Resources” of fifth Framework Programme (no. QLG2-CT-2002-01254).
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Supplementary table 1. Minor allele associated risk for incident coronary heart disease and ischemic stroke event of SNPs rs28665122, rs4965373 and rs9874 (DOC 52 kb)
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Supplementary table 2. Haplotype carriership associated risk of incident coronary heart disease and ischemic stroke event (DOC 43 kb)
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Alanne, M., Kristiansson, K., Auro, K. et al. Variation in the selenoprotein S gene locus is associated with coronary heart disease and ischemic stroke in two independent Finnish cohorts. Hum Genet 122, 355–365 (2007). https://doi.org/10.1007/s00439-007-0402-7
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DOI: https://doi.org/10.1007/s00439-007-0402-7