Research ExplorerPublicationsGenome-Wide Association Study of L-Arginine and Dimethylargi...

Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine

Standard

Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine. / Lüneburg, Nicole; Lieb, Wolfgang; Zeller, Tanja; Chen, Ming-Huei; Maas, Renke; Carter, Angela M; Xanthakis, Vanessa; Glazer, Nicole L; Schwedhelm, Edzard; Seshadri, Sudha; Ikram, M Arfan; Longstreth, W T; Fornage, Myriam; König, Inke R; Loley, Christina; Ojeda Echevarria, Francisco Miguel; Schillert, Arne; Wang, Thomas J; Sticht, Heinrich; Kittel, Anja; König, Jörg; Benjamin, Emelia J; Sullivan, Lisa M; Bernges, Isabel; Anderssohn, Maike; Ziegler, Andreas; Gieger, Christian; Illig, Thomas; Meisinger, Christa; Wichmann, H-Erich; Wild, Philipp S; Schunkert, Heribert; Psaty, Bruce M; Wiggins, Kerri L; Heckbert, Susan R; Smith, Nicholas; Lackner, Karl; Lunetta, Kathryn L; Blankenberg, Stefan; Erdmann, Jeanette; Münzel, Thomas; Grant, Peter J; Vasan, Ramachandran S; Böger, Rainer H.

In: CIRC-CARDIOVASC GENE, 21.09.2014.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lüneburg, N, Lieb, W, Zeller, T, Chen, M-H, Maas, R, Carter, AM, Xanthakis, V, Glazer, NL, Schwedhelm, E, Seshadri, S, Ikram, MA, Longstreth, WT, Fornage, M, König, IR, Loley, C, Ojeda Echevarria, FM, Schillert, A, Wang, TJ, Sticht, H, Kittel, A, König, J, Benjamin, EJ, Sullivan, LM, Bernges, I, Anderssohn, M, Ziegler, A, Gieger, C, Illig, T, Meisinger, C, Wichmann, H-E, Wild, PS, Schunkert, H, Psaty, BM, Wiggins, KL, Heckbert, SR, Smith, N, Lackner, K, Lunetta, KL, Blankenberg, S, Erdmann, J, Münzel, T, Grant, PJ, Vasan, RS & Böger, RH 2014, 'Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine', CIRC-CARDIOVASC GENE. https://doi.org/10.1161/CIRCGENETICS.113.000264

APA

Lüneburg, N., Lieb, W., Zeller, T., Chen, M-H., Maas, R., Carter, A. M., Xanthakis, V., Glazer, N. L., Schwedhelm, E., Seshadri, S., Ikram, M. A., Longstreth, W. T., Fornage, M., König, I. R., Loley, C., Ojeda Echevarria, F. M., Schillert, A., Wang, T. J., Sticht, H., ... Böger, R. H. (2014). Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine. CIRC-CARDIOVASC GENE. https://doi.org/10.1161/CIRCGENETICS.113.000264

Vancouver

Lüneburg N, Lieb W, Zeller T, Chen M-H, Maas R, Carter AM et al. Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine. CIRC-CARDIOVASC GENE. 2014 Sep 21. https://doi.org/10.1161/CIRCGENETICS.113.000264

Bibtex

@article{4df8b953062a407dacd2d98b1f9fec2d,
title = "Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine",
abstract = "BACKGROUND: -Dimethylarginines (DMA) interfere with nitric oxide (NO) formation by inhibiting NO synthase (asymmetric dimethylarginine, ADMA) and L-arginine uptake into the cell (ADMA and symmetric dimethylarginine, SDMA). In prospective clinical studies ADMA has been characterized as a cardiovascular risk marker whereas SDMA is a novel marker for renal function and associated with all-cause mortality after ischemic stroke. The aim of the current study was to characterise the environmental and genetic contributions to inter-individual variability of these biomarkers.METHODS AND RESULTS: -This study comprised a genome-wide association analysis of 3 well-characterized population-based cohorts (FHS (n=2992), GHS (n=4354) and MONICA/KORA F3 (n=581)) and identified replicated loci (DDAH1, MED23, Arg1 and AGXT2) associated with the inter-individual variability in ADMA, L-arginine and SDMA. Experimental in-silico and in-vitro studies confirmed functional significance of the identified AGXT2 variants. Clinical outcome analysis in 384 patients of the Leeds stroke study demonstrated an association between increased plasma levels of SDMA, AGXT2 variants and various cardiometabolic risk factors. AGXT2 variants were not associated with post-stroke survival in the Leeds study, nor were they associated with incident stroke in the CHARGE consortium.CONCLUSIONS: -These GWAS support the importance of DDAH1 and MED23/Arg1 in regulating ADMA and L-arginine metabolism, respectively, and identify a novel regulatory renal pathway for SDMA by AGXT2. AGXT2 variants might explain part of the pathogenic link between SDMA, renal function, and outcome. An association between AGXT2 variants and stroke is unclear and warrants further investigation.",
author = "Nicole L{\"u}neburg and Wolfgang Lieb and Tanja Zeller and Ming-Huei Chen and Renke Maas and Carter, {Angela M} and Vanessa Xanthakis and Glazer, {Nicole L} and Edzard Schwedhelm and Sudha Seshadri and Ikram, {M Arfan} and Longstreth, {W T} and Myriam Fornage and K{\"o}nig, {Inke R} and Christina Loley and {Ojeda Echevarria}, {Francisco Miguel} and Arne Schillert and Wang, {Thomas J} and Heinrich Sticht and Anja Kittel and J{\"o}rg K{\"o}nig and Benjamin, {Emelia J} and Sullivan, {Lisa M} and Isabel Bernges and Maike Anderssohn and Andreas Ziegler and Christian Gieger and Thomas Illig and Christa Meisinger and H-Erich Wichmann and Wild, {Philipp S} and Heribert Schunkert and Psaty, {Bruce M} and Wiggins, {Kerri L} and Heckbert, {Susan R} and Nicholas Smith and Karl Lackner and Lunetta, {Kathryn L} and Stefan Blankenberg and Jeanette Erdmann and Thomas M{\"u}nzel and Grant, {Peter J} and Vasan, {Ramachandran S} and B{\"o}ger, {Rainer H}",
year = "2014",
month = sep,
day = "21",
doi = "10.1161/CIRCGENETICS.113.000264",
language = "English",
journal = "CIRC-CARDIOVASC GENE",
issn = "1942-325X",
publisher = "Lippincott Williams and Wilkins",

}

RIS

TY - JOUR

T1 - Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine

AU - Lüneburg, Nicole

AU - Lieb, Wolfgang

AU - Zeller, Tanja

AU - Chen, Ming-Huei

AU - Maas, Renke

AU - Carter, Angela M

AU - Xanthakis, Vanessa

AU - Glazer, Nicole L

AU - Schwedhelm, Edzard

AU - Seshadri, Sudha

AU - Ikram, M Arfan

AU - Longstreth, W T

AU - Fornage, Myriam

AU - König, Inke R

AU - Loley, Christina

AU - Ojeda Echevarria, Francisco Miguel

AU - Schillert, Arne

AU - Wang, Thomas J

AU - Sticht, Heinrich

AU - Kittel, Anja

AU - König, Jörg

AU - Benjamin, Emelia J

AU - Sullivan, Lisa M

AU - Bernges, Isabel

AU - Anderssohn, Maike

AU - Ziegler, Andreas

AU - Gieger, Christian

AU - Illig, Thomas

AU - Meisinger, Christa

AU - Wichmann, H-Erich

AU - Wild, Philipp S

AU - Schunkert, Heribert

AU - Psaty, Bruce M

AU - Wiggins, Kerri L

AU - Heckbert, Susan R

AU - Smith, Nicholas

AU - Lackner, Karl

AU - Lunetta, Kathryn L

AU - Blankenberg, Stefan

AU - Erdmann, Jeanette

AU - Münzel, Thomas

AU - Grant, Peter J

AU - Vasan, Ramachandran S

AU - Böger, Rainer H

PY - 2014/9/21

Y1 - 2014/9/21

N2 - BACKGROUND: -Dimethylarginines (DMA) interfere with nitric oxide (NO) formation by inhibiting NO synthase (asymmetric dimethylarginine, ADMA) and L-arginine uptake into the cell (ADMA and symmetric dimethylarginine, SDMA). In prospective clinical studies ADMA has been characterized as a cardiovascular risk marker whereas SDMA is a novel marker for renal function and associated with all-cause mortality after ischemic stroke. The aim of the current study was to characterise the environmental and genetic contributions to inter-individual variability of these biomarkers.METHODS AND RESULTS: -This study comprised a genome-wide association analysis of 3 well-characterized population-based cohorts (FHS (n=2992), GHS (n=4354) and MONICA/KORA F3 (n=581)) and identified replicated loci (DDAH1, MED23, Arg1 and AGXT2) associated with the inter-individual variability in ADMA, L-arginine and SDMA. Experimental in-silico and in-vitro studies confirmed functional significance of the identified AGXT2 variants. Clinical outcome analysis in 384 patients of the Leeds stroke study demonstrated an association between increased plasma levels of SDMA, AGXT2 variants and various cardiometabolic risk factors. AGXT2 variants were not associated with post-stroke survival in the Leeds study, nor were they associated with incident stroke in the CHARGE consortium.CONCLUSIONS: -These GWAS support the importance of DDAH1 and MED23/Arg1 in regulating ADMA and L-arginine metabolism, respectively, and identify a novel regulatory renal pathway for SDMA by AGXT2. AGXT2 variants might explain part of the pathogenic link between SDMA, renal function, and outcome. An association between AGXT2 variants and stroke is unclear and warrants further investigation.

AB - BACKGROUND: -Dimethylarginines (DMA) interfere with nitric oxide (NO) formation by inhibiting NO synthase (asymmetric dimethylarginine, ADMA) and L-arginine uptake into the cell (ADMA and symmetric dimethylarginine, SDMA). In prospective clinical studies ADMA has been characterized as a cardiovascular risk marker whereas SDMA is a novel marker for renal function and associated with all-cause mortality after ischemic stroke. The aim of the current study was to characterise the environmental and genetic contributions to inter-individual variability of these biomarkers.METHODS AND RESULTS: -This study comprised a genome-wide association analysis of 3 well-characterized population-based cohorts (FHS (n=2992), GHS (n=4354) and MONICA/KORA F3 (n=581)) and identified replicated loci (DDAH1, MED23, Arg1 and AGXT2) associated with the inter-individual variability in ADMA, L-arginine and SDMA. Experimental in-silico and in-vitro studies confirmed functional significance of the identified AGXT2 variants. Clinical outcome analysis in 384 patients of the Leeds stroke study demonstrated an association between increased plasma levels of SDMA, AGXT2 variants and various cardiometabolic risk factors. AGXT2 variants were not associated with post-stroke survival in the Leeds study, nor were they associated with incident stroke in the CHARGE consortium.CONCLUSIONS: -These GWAS support the importance of DDAH1 and MED23/Arg1 in regulating ADMA and L-arginine metabolism, respectively, and identify a novel regulatory renal pathway for SDMA by AGXT2. AGXT2 variants might explain part of the pathogenic link between SDMA, renal function, and outcome. An association between AGXT2 variants and stroke is unclear and warrants further investigation.

U2 - 10.1161/CIRCGENETICS.113.000264

DO - 10.1161/CIRCGENETICS.113.000264

M3 - SCORING: Journal article

C2 - 25245031

JO - CIRC-CARDIOVASC GENE

JF - CIRC-CARDIOVASC GENE

SN - 1942-325X

ER -