title: Matrix gla protein gene polymorphism is associated with increased coronary artery calcification progression.
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.
  
  
  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: Department of Public Health Sciences, Henry Ford Hospital, One Ford Place, Detroit, MI, USA.
authors: Andrea E
authors: AE
authors: Cassidy-Bushrow
authors: Lawrence F
authors: LF
authors: Bielak
authors: Albert M
authors: AM
authors: Levin
authors: Patrick F
authors: PF
authors: Sheedy
authors: Stephen T
authors: ST
authors: Turner
authors: Eric
authors: E
authors: Boerwinkle
authors: Xihong
authors: X
authors: Lin
authors: Sharon L R
authors: SL
authors: Kardia
authors: Patricia A
authors: PA
authors: Peyser
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002135:Calcium-Binding Proteins / Q000235:genetics*; D016009:Chi-Square Distribution; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D061205:Vascular Calcification / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D000097568:Matrix Gla Protein
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein