Inactive Matrix Gla Protein Is Causally Related to Adverse Health Outcomes A Mendelian Randomization Study in a Flemish Population

Yan-Ping Liu, Yu-Mei Gu, Lutgarde Thijs, Marjo H. J. Knapen, Erika Salvi, Lorena Citterio, Thibault Petit, Simona Delli Carpini, Zhenyu Zhang, Lotte Jacobs, Yu Jin, Cristina Barlassina, Paolo Manunta, Tatiana Kuznetsova, Peter Verhamme, Harry A. Struijker-Boudier, Daniele Cusi, Cees Vermeer, Jan A. Staessen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Matrix Gla-protein is a vitamin K-dependent protein that strongly inhibits arterial calcification. Vitamin K deficiency leads to production of inactive nonphosphorylated and uncarboxylated matrix Gla protein (dp-ucMGP). The risk associated with dp-ucMGP in the population is unknown. In a Flemish population study, we measured circulating dp-ucMGP at baseline (1996-2011), genotyped MGP, recorded adverse health outcomes until December 31, 2012, and assessed the multivariable-adjusted associations of adverse health outcomes with dp-ucMGP. We applied a Mendelian randomization analysis using MGP genotypes as instrumental variables. Among 2318 participants, baseline dp-ucMGP averaged 3.61 mu g/L. Over 14.1 years (median), 197 deaths occurred, 58 from cancer and 70 from cardiovascular disease; 85 participants experienced a coronary event. The risk of death and non-cancer mortality curvilinearly increased (P = 0.13), the Mendelian randomization analysis suggested causality. Higher dp-ucMGP predicts total, non-cancer and cardiovascular mortality, but lower coronary risk. For non-cancer mortality and coronary events, these associations are likely causal.
Original languageEnglish
Pages (from-to)463-U497
Issue number2
Publication statusPublished - Feb 2015


  • matrix Gla protein
  • Mendelian randomization
  • mortality

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