Adrenomedullin and arterial stiffness: integrative approach combining monocyte ADM expression, plasma MR-Pro-ADM, and genome-wide association study
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Adrenomedullin and arterial stiffness: integrative approach combining monocyte ADM expression, plasma MR-Pro-ADM, and genome-wide association study. / Beygui, Farzin; Wild, Philipp S; Zeller, Tanja; Germain, Marine; Castagné, Raphaele; Lackner, Karl J; Münzel, Thomas; Montalescot, Gilles; Mitchell, Gary F; Verwoert, Germaine C; Tarasov, Kirill V; Trégouët, David-Alexandre; Cambien, François; Blankenberg, Stefan; Tiret, Laurence.
In: CIRC-CARDIOVASC GENE, Vol. 7, No. 5, 10.2014, p. 634-641.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Adrenomedullin and arterial stiffness: integrative approach combining monocyte ADM expression, plasma MR-Pro-ADM, and genome-wide association study
AU - Beygui, Farzin
AU - Wild, Philipp S
AU - Zeller, Tanja
AU - Germain, Marine
AU - Castagné, Raphaele
AU - Lackner, Karl J
AU - Münzel, Thomas
AU - Montalescot, Gilles
AU - Mitchell, Gary F
AU - Verwoert, Germaine C
AU - Tarasov, Kirill V
AU - Trégouët, David-Alexandre
AU - Cambien, François
AU - Blankenberg, Stefan
AU - Tiret, Laurence
N1 - © 2014 American Heart Association, Inc.
PY - 2014/10
Y1 - 2014/10
N2 - BACKGROUND: Adrenomedullin (ADM) is a circulating vasoactive peptide involved in vascular homeostasis and endothelial function. Single nucleotide polymorphisms of the ADM gene are associated with blood pressure variability, and elevated levels of plasma midregional proadrenomedullin (MR-pro-ADM) are associated with cardiovascular diseases.METHODS AND RESULTS: We investigated the sources of variability of ADM gene expression and plasma MR-pro-ADM concentrations in the general population, and their relationship with markers of atherosclerosis. MR-pro-ADM levels were assessed in 4155 individuals who underwent evaluation of carotid intima-media thickness and arterial rigidity (reflection index and stiffness index). In a subsample of 1372 individuals, ADM gene expression was assessed as part of a transcriptomic study of circulating monocytes. Nongenetic factors explained 45.8% and 7.5% of MR-pro-ADM and ADM expression variability, respectively. ADM expression correlated with plasma C-reactive protein, interleukin-receptor 1A, and myeloperoxidase, whereas MR-pro-ADM levels correlated with C-terminal proendothelin-1, creatinine, and N-terminal pro-B-type natriuretic peptide. Genome-wide association study of ADM expression and MR-pro-ADM levels both identified a single locus encompassing the ADM gene. ADM expression was associated with 1 single nucleotide polymorphism rs11042717 (P=2.36×10(-12)), whereas MR-pro-ADM was associated with 2 single nucleotide polymorphisms with additive effects, rs2957692 (P=1.54×10(-13)) and rs2957717 (P=4.24×10(-8)). Reflection index was independently associated with rs11042717 (P<10(-4)) and ADM expression (P=0.0002) but not with MR-pro-ADM. Weaker associations were observed for stiffness index. Intima-media thickness was not related to ADM single nucleotide polymorphisms or expression.CONCLUSIONS: These results support an involvement of the ADM gene in the modulation of peripheral vascular tone.
AB - BACKGROUND: Adrenomedullin (ADM) is a circulating vasoactive peptide involved in vascular homeostasis and endothelial function. Single nucleotide polymorphisms of the ADM gene are associated with blood pressure variability, and elevated levels of plasma midregional proadrenomedullin (MR-pro-ADM) are associated with cardiovascular diseases.METHODS AND RESULTS: We investigated the sources of variability of ADM gene expression and plasma MR-pro-ADM concentrations in the general population, and their relationship with markers of atherosclerosis. MR-pro-ADM levels were assessed in 4155 individuals who underwent evaluation of carotid intima-media thickness and arterial rigidity (reflection index and stiffness index). In a subsample of 1372 individuals, ADM gene expression was assessed as part of a transcriptomic study of circulating monocytes. Nongenetic factors explained 45.8% and 7.5% of MR-pro-ADM and ADM expression variability, respectively. ADM expression correlated with plasma C-reactive protein, interleukin-receptor 1A, and myeloperoxidase, whereas MR-pro-ADM levels correlated with C-terminal proendothelin-1, creatinine, and N-terminal pro-B-type natriuretic peptide. Genome-wide association study of ADM expression and MR-pro-ADM levels both identified a single locus encompassing the ADM gene. ADM expression was associated with 1 single nucleotide polymorphism rs11042717 (P=2.36×10(-12)), whereas MR-pro-ADM was associated with 2 single nucleotide polymorphisms with additive effects, rs2957692 (P=1.54×10(-13)) and rs2957717 (P=4.24×10(-8)). Reflection index was independently associated with rs11042717 (P<10(-4)) and ADM expression (P=0.0002) but not with MR-pro-ADM. Weaker associations were observed for stiffness index. Intima-media thickness was not related to ADM single nucleotide polymorphisms or expression.CONCLUSIONS: These results support an involvement of the ADM gene in the modulation of peripheral vascular tone.
KW - Adrenomedullin/blood
KW - Adult
KW - Aged
KW - Atherosclerosis/blood
KW - Carotid Arteries/diagnostic imaging
KW - Carotid Intima-Media Thickness
KW - Cohort Studies
KW - Female
KW - Gene Expression Profiling
KW - Gene Expression Regulation
KW - Genetic Variation
KW - Genome-Wide Association Study
KW - Genotype
KW - Humans
KW - Linear Models
KW - Male
KW - Middle Aged
KW - Monocytes/cytology
KW - Polymorphism, Single Nucleotide
KW - Protein Precursors/blood
KW - Transcription, Genetic
KW - Transcriptome
KW - Vascular Stiffness/genetics
U2 - 10.1161/CIRCGENETICS.113.000456
DO - 10.1161/CIRCGENETICS.113.000456
M3 - SCORING: Journal article
C2 - 25053723
VL - 7
SP - 634
EP - 641
JO - CIRC-CARDIOVASC GENE
JF - CIRC-CARDIOVASC GENE
SN - 1942-325X
IS - 5
ER -
