title: Polymorphisms in the Selenoprotein S gene and subclinical cardiovascular disease in the Diabetes Heart Study.
abstract: Selenoprotein S (SelS) has previously been associated with a range of inflammatory markers, particularly in the context of cardiovascular disease (CVD). The aim of this study was to examine the role of SELS genetic variants in risk for subclinical CVD and mortality in individuals with type 2 diabetes mellitus (T2DM). The association between 10 polymorphisms tagging SELS and coronary (CAC), carotid (CarCP) and abdominal aortic calcified plaque, carotid intima media thickness and other known CVD risk factors was examined in 1220 European Americans from the family-based Diabetes Heart Study. The strongest evidence of association for SELS SNPs was observed for CarCP; rs28665122 (5' region; β = 0.329, p = 0.044), rs4965814 (intron 5; β = 0.329, p = 0.036), rs28628459 (3' region; β = 0.331, p = 0.039) and rs7178239 (downstream; β = 0.375, p = 0.016) were all associated. In addition, rs12917258 (intron 5) was associated with CAC (β = -0.230, p = 0.032), and rs4965814, rs28628459 and rs9806366 were all associated with self-reported history of prior CVD (p = 0.020-0.043). These results suggest a potential role for the SELS region in the development subclinical CVD in this sample enriched for T2DM. Further understanding the mechanisms underpinning these relationships may prove important in predicting and managing CVD complications in T2DM.
authors.affiliation: Center for Human Genomics, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cox
authors.forename: Allison B
authors.initials: AB
authors.lastname: Lehtinen
authors.forename: Jianzhao
authors.initials: J
authors.lastname: Xu
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D002340:Carotid Artery Diseases / Q000453:epidemiology / Q000235:genetics; D059168:Carotid Intima-Media Thickness; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051140:Selenoproteins / Q000235:genetics*; D061205:Vascular Calcification / Q000453:epidemiology / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C487710:SELENOS protein, human; D051140:Selenoproteins