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.

Trial registration: ClinicalTrials.gov NCT00183001.

Conflict of interest statement

Author disclosures: M. K. Shea, C. J. O’Donnell, M. D. Crosier, C. M. Gundberg, J. M. Ordovas, S. B. Kritchevsky, and S. L. Booth, no conflicts of interest. C. Vermeer is CEO of VitaK BV and E. J. P. Magdeleyns is employed by VitaK BV.

Figures

FIGURE 1

Changes in plasma ucMGP concentration in 190 older adults who received 500 μg/d phylloquinone for 3 y and 184 who did not. Values are mean ± SD. *The changes, adjusted for baseline plasma ucMGP, differed, P < 0.0001.