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

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 gen... Mehr ...

Verfasser: Liu, Yan-Ping
Gu, Yu-Mei
Thijs, Lutgarde
Knapen, Marjo H. J.
Salvi, Erika
Citterio, Lorena
Petit, Thibault
Carpini, Simona Delli
Zhang, Zhenyu
Jacobs, Lotte
Jin, Yu
Barlassina, Cristina
Manunta, Paolo
Kuznetsova, Tatiana
Verhamme, Peter
Struijker-Boudier, Harry A.
Cusi, Daniele
Vermeer, Cees
Staessen, Jan A.
Dokumenttyp: Artikel
Erscheinungsdatum: 2015
Reihe/Periodikum: Liu , Y-P , Gu , Y-M , Thijs , L , Knapen , M H J , Salvi , E , Citterio , L , Petit , T , Carpini , S D , Zhang , Z , Jacobs , L , Jin , Y , Barlassina , C , Manunta , P , Kuznetsova , T , Verhamme , P , Struijker-Boudier , H A , Cusi , D , Vermeer , C & Staessen , J A 2015 , ' Inactive Matrix Gla Protein Is Causally Related to Adverse Health Outcomes A Mendelian Randomization Study in a Flemish Population ' , Hypertension , vol. 65 , no. 2 , pp. 463-U497 . https://doi.org/10.1161/HYPERTENSIONAHA.114.04494
Schlagwörter: matrix Gla protein / Mendelian randomization / mortality
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29064567
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://cris.maastrichtuniversity.nl/en/publications/19ce919f-870b-461e-a52b-8874089355ce

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.