title: Association of alpha2-Heremans-Schmid glycoprotein polymorphisms with subclinical atherosclerosis.
abstract: BACKGROUND
  Cardiovascular disease is significantly increased in individuals with type 2 diabetes mellitus (T2DM), especially in the presence of calcified atherosclerotic plaque. Fetuin A is an important mineralization inhibitor, and polymorphisms in the corresponding alpha2-Heremans-Schmid glycoprotein (AHSG) gene have been shown to be associated with serum fetuin A levels and free phosphate levels, as well as cardiovascular disease death.
  
  
  OBJECTIVE
  This study investigated whether polymorphisms in AHSG contribute to the development of calcified atherosclerotic plaque in the coronary and carotid arteries and to carotid artery intima-media thickness.
  
  
  METHODS
  Eleven single nucleotide polymorphisms (SNPs) in AHSG were genotyped and evaluated for association with quantitative measures of subclinical atherosclerosis.
  
  
  METHODS
  Subjects were 829 T2DM-affected European Americans from 368 families in the Diabetes Heart Study.
  
  
  METHODS
  Participants were phenotyped for cardiovascular risk factors and atherosclerosis traits. The extent of coronary artery calcified plaque (CorCP) and carotid artery calcified plaque (CarCP) was measured using quantitative computed tomography, and carotid artery intima-media thickness was measured using high-resolution B mode ultrasonography.
  
  
  RESULTS
  Four SNPs in AHSG were nominally associated with CorCP in European Americans with T2DM (P < 0.05). Two 3-SNP haplotypes in the exon 6-7 region were associated with CorCP in European Americans with T2DM (P < 0.06).
  
  
  CONCLUSIONS
  Sequence variants in the AHSG gene affect the extent of CorCP in T2DM-affected European Americans, consistent with the known biological role of AHSG in vascular calcification. These data implicate AHSG in the development of vascular calcified plaque in diabetic subjects.
authors.affiliation: Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
authors.forename: Allison B
authors.initials: AB
authors.lastname: Lehtinen
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Lewis
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Julie T
authors.initials: JT
authors.lastname: Ziegler
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology* / Q000235:genetics; D001798:Blood Proteins / Q000032:analysis / Q000235:genetics*; D002114:Calcinosis / Q000097:blood / Q000209:etiology* / Q000235:genetics; D002340:Carotid Artery Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics; D003327:Coronary Disease / Q000097:blood / Q000209:etiology* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000097:blood / Q000209:etiology* / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060749:alpha-2-HS-Glycoprotein
chemical_list: C556354:AHSG protein, human; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein