TY - JOUR
T1 - Inactive Matrix Gla Protein Is Causally Related to Adverse Health Outcomes A Mendelian Randomization Study in a Flemish Population
AU - Liu, Yan-Ping
AU - Gu, Yu-Mei
AU - Thijs, Lutgarde
AU - Knapen, Marjo H. J.
AU - Salvi, Erika
AU - Citterio, Lorena
AU - Petit, Thibault
AU - Carpini, Simona Delli
AU - Zhang, Zhenyu
AU - Jacobs, Lotte
AU - Jin, Yu
AU - Barlassina, Cristina
AU - Manunta, Paolo
AU - Kuznetsova, Tatiana
AU - Verhamme, Peter
AU - Struijker-Boudier, Harry A.
AU - Cusi, Daniele
AU - Vermeer, Cees
AU - Staessen, Jan A.
PY - 2015/2
Y1 - 2015/2
N2 - 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.
AB - 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.
KW - matrix Gla protein
KW - Mendelian randomization
KW - mortality
U2 - 10.1161/HYPERTENSIONAHA.114.04494
DO - 10.1161/HYPERTENSIONAHA.114.04494
M3 - Article
C2 - 25421980
SN - 0194-911X
VL - 65
SP - 463-U497
JO - Hypertension
JF - Hypertension
IS - 2
ER -