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| PMID |
|
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| TITLE |
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| Metabolomics reveals a link between homocysteine and lipid metabolism and leukocyte telomere length: the ENGAGE consortium. |
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| ABSTRACT |
|
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| Telomere shortening has been associated with multiple age-related diseases such as cardiovascular disease, diabetes, and dementia. However, the biological mechanisms responsible for these associations remain largely unknown. In order to gain insight into the metabolic processes driving the association of leukocyte telomere length (LTL) with age-related diseases, we investigated the association between LTL and serum metabolite levels in 7,853 individuals from seven independent cohorts. LTL was determined by quantitative polymerase chain reaction and the levels of 131 serum metabolites were measured with mass spectrometry in biological samples from the same blood draw. With partial correlation analysis, we identified six metabolites that were significantly associated with LTL after adjustment for multiple testing: lysophosphatidylcholine acyl C17:0 (lysoPC a C17:0, p-value = 7.1 × 10 ), methionine (p-value = 9.2 × 10 ), tyrosine (p-value = 2.1 × 10 ), phosphatidylcholine diacyl C32:1 (PC aa C32:1, p-value = 2.4 × 10 ), hydroxypropionylcarnitine (C3-OH, p-value = 2.6 × 10 ), and phosphatidylcholine acyl-alkyl C38:4 (PC ae C38:4, p-value = 9.0 × 10 ). Pathway analysis showed that the three phosphatidylcholines and methionine are involved in homocysteine metabolism and we found supporting evidence for an association of lipid metabolism with LTL. In conclusion, we found longer LTL associated with higher levels of lysoPC a C17:0 and PC ae C38:4, and with lower levels of methionine, tyrosine, PC aa C32:1, and C3-OH. These metabolites have been implicated in inflammation, oxidative stress, homocysteine metabolism, and in cardiovascular disease and diabetes, two major drivers of morbidity and mortality. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2018/09/11 |
| accepted |
2019/06/26 |
| entrez |
2019/08/14 06:00 |
| pubmed |
2019/08/14 06:00 |
| medline |
2020/11/11 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| van der Spek A |
|
van der Spek |
Ashley |
A |
|
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. |
| Broer L |
|
Broer |
Linda |
L |
|
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. |
| Draisma HHM |
|
Draisma |
Harmen H M |
HHM |
|
Section of Genomics of Common Disease, Imperial College London, Burlington Danes Building Room E301, Du Cane Road, London, W12 0NN, UK. |
| Pool R |
|
Pool |
René |
R |
|
BBMRI-NL: Infrastructure for the Application of Metabolomics Technology in Epidemiology (RP4), Utrecht, The Netherlands. |
| Albrecht E |
|
Albrecht |
Eva |
E |
|
Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. |
| Beekman M |
|
Beekman |
Marian |
M |
|
Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands. |
| Mangino M |
|
Mangino |
Massimo |
M |
|
NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, SE1 9RT, UK. |
| Raag M |
|
Raag |
Mait |
M |
|
Institute of Family Medicine and Public Health, University of Tartu, Tartu, Estonia. |
| Nyholt DR |
|
Nyholt |
Dale R |
DR |
|
School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. |
| Dharuri HK |
|
Dharuri |
Harish K |
HK |
|
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. |
| Codd V |
|
Codd |
Veryan |
V |
|
Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK. |
| Amin N |
|
Amin |
Najaf |
N |
|
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. |
| de Geus EJC |
|
de Geus |
Eco J C |
EJC |
|
Amsterdam Public Health research institute, Amsterdam University Medical Centers, Amsterdam, The Netherlands. |
| Deelen J |
|
Deelen |
Joris |
J |
|
Max Planck Institute for Biology of Ageing, Cologne, Germany. |
| Demirkan A |
|
Demirkan |
Ayse |
A |
|
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. |
| Yet I |
|
Yet |
Idil |
I |
|
Department of Bioinformatics, Institute of Health Sciences, Hacettepe University, 06100, Ankara, Turkey. |
| Fischer K |
|
Fischer |
Krista |
K |
|
Institute of Mathematics and Statistics, University of Tartu, Tartu, Estonia. |
| Haller T |
|
Haller |
Toomas |
T |
|
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia. |
| Henders AK |
|
Henders |
Anjali K |
AK |
|
The Institute for Molecular Biosciences, The University of Queensland, Brisbane, Australia. |
| Isaacs A |
|
Isaacs |
Aaron |
A |
|
CARIM School for Cardiovascular Diseases, Maastricht Centre for Systems Biology (MaCSBio), and Department of Biochemistry, Maastricht University, Maastricht, The Netherlands. |
| Medland SE |
|
Medland |
Sarah E |
SE |
|
QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
| Mooijaart SP |
|
Mooijaart |
Simon P |
SP |
|
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. |
| Strauch K |
|
Strauch |
Konstantin |
K |
|
Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Germany. |
| Suchiman HED |
|
Suchiman |
H Eka D |
HED |
|
Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands. |
| Vaarhorst AAM |
|
Vaarhorst |
Anika A M |
AAM |
|
Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands. |
| van Heemst D |
|
van Heemst |
Diana |
D |
|
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. |
| Wang-Sattler R |
|
Wang-Sattler |
Rui |
R |
|
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. |
| Whitfield JB |
|
Whitfield |
John B |
JB |
|
QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
| Willemsen G |
|
Willemsen |
Gonneke |
G |
|
Amsterdam Public Health research institute, Amsterdam University Medical Centers, Amsterdam, The Netherlands. |
| Wright MJ |
|
Wright |
Margaret J |
MJ |
|
Queensland Brain Institute, The University of Queensland, Brisbane, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
| Samani NJ |
|
Samani |
Nilesh J |
NJ |
|
Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK. |
| Metspalu A |
|
Metspalu |
Andres |
A |
|
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia. |
| Eline Slagboom P |
|
Eline Slagboom |
P |
P |
|
Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands. |
| Spector TD |
|
Spector |
Tim D |
TD |
|
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. |
| Boomsma DI |
|
Boomsma |
Dorret I |
DI |
|
BBMRI-NL: Infrastructure for the Application of Metabolomics Technology in Epidemiology (RP4), Utrecht, The Netherlands. |
| van Duijn CM |
|
van Duijn |
Cornelia M |
CM |
|
Nuffield Department of Population Health, University of Oxford, Oxford, UK. c.vanduijn@erasmusmc.nl. |
| Gieger C |
|
Gieger |
Christian |
C |
|
Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. |
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 9 |
| ISSUE: 1 |
| TITLE: Scientific reports |
| ISOABBREVIATION: Sci Rep |
| YEAR: 2019 |
| MONTH: 08 |
| DAY: 12 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 2045-2322 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
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| MEDLINETA: Sci Rep |
| COUNTRY: England |
| ISSNLINKING: 2045-2322 |
| NLMUNIQUEID: 101563288 |
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| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, Non-U.S. Gov't |
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| COMMENTS AND CORRECTIONS |
|
|
| GRANTS |
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| GRANTID |
AGENCY |
COUNTRY |
|
Wellcome Trust |
United Kingdom |
|
Medical Research Council |
United Kingdom |
| 619667 |
Department of Health |
United Kingdom |
| WT205915 |
Wellcome Trust |
United Kingdom |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adult |
|
| Aged |
|
| Cohort Studies |
|
| Female |
|
| Homocysteine |
metabolism |
| Humans |
metabolism |
| Leukocytes |
ultrastructure |
| Lipid Metabolism |
ultrastructure |
| Male |
ultrastructure |
| Metabolomics |
methods |
| Middle Aged |
methods |
| Telomere |
methods |
| Telomere Shortening |
methods |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0LVT1QZ0BA |
Homocysteine |
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| OTHER ID's |
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|
