Document Detail


Matrix gla protein gene polymorphism is associated with increased coronary artery calcification progression.
MedLine Citation:
PMID:  23307874     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Matrix gla protein (MGP) inhibits arterial and cartilaginous calcification. A threonine to alanine (Thr83Ala) polymorphism (codon 83) in MGP is associated with myocardial infarction and femoral artery calcification. We examined the association of the MGP Thr83Ala polymorphism with quantity and progression of coronary artery calcification (CAC), a noninvasive measure of subclinical coronary atherosclerosis.
METHODS AND RESULTS: In 605 participants of the Epidemiology of Coronary Artery Calcification Study, generalized linear mixed models were fit to determine the association of MGP Thr83Ala with CAC quantity and progression. There was a significant additive relation between MGP Thr83Ala and CAC progression (P=0.001). In the fully adjusted model, every 1 Ala83 allele increase was associated with an estimated 1.9% (95% confidence interval, 0.7%-3.0%) per year since baseline larger increase in CAC quantity. A proxy single nucleotide polymorphism for MGP Thr83Ala (rs6488724) was similarly associated with CAC progression in an independent cohort from the Genetic Epidemiology Network of Arteriopathy (GENOA) study.
CONCLUSIONS: Increased risk of myocardial infarction associated with MGP ThrAla83 genotype observed elsewhere may be related to faster progression of subclinical coronary atherosclerosis. MGP genotype could be a potential candidate for identifying individuals at increased risk of atherosclerotic disease who would benefit from aggressive primary prevention strategies.
Authors:
Andrea E Cassidy-Bushrow; Lawrence F Bielak; Albert M Levin; Patrick F Sheedy; Stephen T Turner; Eric Boerwinkle; Xihong Lin; Sharon L R Kardia; Patricia A Peyser
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-10
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  33     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-14     Completed Date:  2013-04-10     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  645-51     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Amino Acid Substitution
Calcium-Binding Proteins / genetics*
Chi-Square Distribution
Coronary Angiography / methods
Coronary Artery Disease / epidemiology,  genetics*,  radiography
Disease Progression
Extracellular Matrix Proteins / genetics*
Female
Gene Frequency
Genetic Predisposition to Disease
Humans
Linear Models
Male
Middle Aged
Minnesota / epidemiology
Myocardial Infarction / epidemiology,  genetics
Phenotype
Polymorphism, Single Nucleotide*
Prevalence
Risk Factors
Time Factors
Tomography, X-Ray Computed
Vascular Calcification / epidemiology,  genetics*,  radiography
Grant Support
ID/Acronym/Agency:
M01-RR00585/RR/NCRR NIH HHS; R01 HL046292/HL/NHLBI NIH HHS; R01 HL08766/HL/NHLBI NIH HHS; R01 HL087660/HL/NHLBI NIH HHS; R01 HL46292/HL/NHLBI NIH HHS; U01 HL054457/HL/NHLBI NIH HHS; U10-HL54457/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/Extracellular Matrix Proteins; 0/matrix Gla protein
Comments/Corrections

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