Matrix gla protein gene polymorphism is associated with increased coronary artery calcification progression

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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. Conclusion-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.

Original languageEnglish (US)
Pages (from-to)645-651
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume33
Issue number3
DOIs
StatePublished - Mar 2013

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Coronary Vessels
Genes
Coronary Artery Disease
Myocardial Infarction
Genotype
Molecular Epidemiology
matrix Gla protein
Proxy
Threonine
Femoral Artery
Primary Prevention
Codon
Alanine
Single Nucleotide Polymorphism
Linear Models
Epidemiology
Alleles
Confidence Intervals

Keywords

  • atherosclerosis
  • calcium
  • genetics
  • imaging
  • population

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Matrix gla protein gene polymorphism is associated with increased coronary artery calcification progression. / Cassidy-Bushrow, Andrea E.; Bielak, Lawrence F.; Levin, Albert M.; Sheedy, Patrick F.; Turner, Stephen T; Boerwinkle, Eric; Lin, Xihong; Kardia, Sharon L R; Peyser, Patricia A.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 33, No. 3, 03.2013, p. 645-651.

Research output: Contribution to journalArticle

Cassidy-Bushrow, AE, Bielak, LF, Levin, AM, Sheedy, PF, Turner, ST, Boerwinkle, E, Lin, X, Kardia, SLR & Peyser, PA 2013, 'Matrix gla protein gene polymorphism is associated with increased coronary artery calcification progression', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 33, no. 3, pp. 645-651. https://doi.org/10.1161/ATVBAHA.112.300491
Cassidy-Bushrow, Andrea E. ; Bielak, Lawrence F. ; Levin, Albert M. ; Sheedy, Patrick F. ; Turner, Stephen T ; Boerwinkle, Eric ; Lin, Xihong ; Kardia, Sharon L R ; Peyser, Patricia A. / Matrix gla protein gene polymorphism is associated with increased coronary artery calcification progression. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2013 ; Vol. 33, No. 3. pp. 645-651.
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