Association of alpha2-Heremans-Schmid glycoprotein polymorphisms with subclinical atherosclerosis.
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.
Lehtinen
Allison B
AB
Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Burdon
Kathryn P
KP
Lewis
Joshua P
JP
Langefeld
Carl D
CD
Ziegler
Julie T
JT
Rich
Stephen S
SS
Register
Thomas C
TC
Carr
J Jeffrey
JJ
Freedman
Barry I
BI
Bowden
Donald W
DW
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
C556354:AHSG protein, human; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein