title: Circulating uncarboxylated matrix gla protein is associated with vitamin K nutritional status, but not coronary artery calcium, in older adults.
abstract: Matrix Gla protein (MGP) is a calcification inhibitor in vascular tissue that must be carboxylated by vitamin K to function. Evidence suggests circulating uncarboxylated MGP (ucMGP) is elevated in persons with disease characterized by vascular calcification. The primary purpose of this study was to determine cross-sectional and longitudinal associations between plasma ucMGP, vitamin K status, and coronary artery calcium (CAC) in older adults without coronary heart disease. Genetic determinants of ucMGP were also explored. Cross-sectional associations among baseline plasma ucMGP, vitamin K status biomarkers [plasma phylloquinone, uncarboxylated prothrombin (PIVKA-II), serum uncarboxylated osteocalcin (%ucOC)], CAC, and plausible genetic polymorphisms were examined in 438 community-dwelling adults (60-80 y, 59% women). The effect of phylloquinone supplementation (500 μg/d) for 3 y on plasma ucMGP was determined among 374 participants. At baseline, plasma phylloquinone was lower and %ucOC and PIVKA-II were greater across higher plasma ucMGP quartiles (all P < 0.001, age-adjusted). Major allele homozygotes for MGP rs1800801 and rs4236 had higher plasma ucMGP than heterozygotes or minor allele homozygotes. (P ≤ 0.004). The decrease in plasma ucMGP was greater in the 190 participants who received phylloquinone (mean ± SD) (-345 ± 251 pmol/L) than in the 184 who did not (-40 ± 196 pmol/L) (P < 0.0001). CAC did not differ according to ucMGP quartile (P = 0.35, age-adjusted). In the phylloquinone-supplemented group, the 3-y change in ucMGP was not associated with the 3-y change in CAC [unstandard β (SE) = -0.02 (0.02); P = 0.44]. Plasma ucMGP was associated with vitamin K status biomarkers and was reduced following phylloquinone supplementation, suggesting it may be a useful marker of vitamin K status in vascular tissue. Plasma ucMGP did not reflect CAC in healthy older adults.
authors.affiliation: Sticht Center on Aging, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: M Kyla
authors.initials: MK
authors.lastname: Shea
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
authors.forename: Elke J P
authors.initials: EJ
authors.lastname: Magdeleyns
authors.forename: Michael D
authors.initials: MD
authors.lastname: Crosier
authors.forename: Caren M
authors.initials: CM
authors.lastname: Gundberg
authors.forename: José M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kritchevsky
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Booth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000097:blood*; D003331:Coronary Vessels / Q000378:metabolism*; D003430:Cross-Sectional Studies; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D014812:Vitamin K / Q000097:blood*; D000097568:Matrix Gla Protein
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D014812:Vitamin K; D000097568:Matrix Gla Protein