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Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

We used Mendelian randomization to estimate the causal effects of the liver enzymes, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT), on diabetes and cardiovascular disease, using genetic variants predicting these liver enzymes at genome wide significan...

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Autores principales: Liu, Junxi, Au Yeung, Shiu Lun, Lin, Shi Lin, Leung, Gabriel M., Schooling, C. Mary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5171875/
https://www.ncbi.nlm.nih.gov/pubmed/27996050
http://dx.doi.org/10.1038/srep38813
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author Liu, Junxi
Au Yeung, Shiu Lun
Lin, Shi Lin
Leung, Gabriel M.
Schooling, C. Mary
author_facet Liu, Junxi
Au Yeung, Shiu Lun
Lin, Shi Lin
Leung, Gabriel M.
Schooling, C. Mary
author_sort Liu, Junxi
collection PubMed
description We used Mendelian randomization to estimate the causal effects of the liver enzymes, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT), on diabetes and cardiovascular disease, using genetic variants predicting these liver enzymes at genome wide significance applied to extensively genotyped case-control studies of diabetes (DIAGRAM) and coronary artery disease (CAD)/myocardial infarction (MI) (CARDIoGRAMplusC4D 1000 Genomes). Genetically higher ALT was associated with higher risk of diabetes, odds ratio (OR) 2.99 per 100% change in concentration (95% confidence interval (CI) 1.62 to 5.52) but ALP OR 0.92 (95% CI 0.71 to 1.19) and GGT OR 0.88 (95% CI 0.75 to 1.04) were not. Genetically predicted ALT, ALP and GGT were not clearly associated with CAD/MI (ALT OR 0.74, 95% CI 0.54 to 1.01, ALP OR 0.86, 95% CI 0.64 to 1.16 and GGT OR 1.08, 95% CI 0.97 to 1.19). We confirm observations of ALT increasing the risk of diabetes, but cannot exclude the possibility that higher ALT may protect against CAD/MI. We also cannot exclude the possibility that GGT increases the risk of CAD/MI and reduces the risk of diabetes. Informative explanations for these potentially contradictory associations should be sought.
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spelling pubmed-51718752016-12-28 Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study Liu, Junxi Au Yeung, Shiu Lun Lin, Shi Lin Leung, Gabriel M. Schooling, C. Mary Sci Rep Article We used Mendelian randomization to estimate the causal effects of the liver enzymes, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT), on diabetes and cardiovascular disease, using genetic variants predicting these liver enzymes at genome wide significance applied to extensively genotyped case-control studies of diabetes (DIAGRAM) and coronary artery disease (CAD)/myocardial infarction (MI) (CARDIoGRAMplusC4D 1000 Genomes). Genetically higher ALT was associated with higher risk of diabetes, odds ratio (OR) 2.99 per 100% change in concentration (95% confidence interval (CI) 1.62 to 5.52) but ALP OR 0.92 (95% CI 0.71 to 1.19) and GGT OR 0.88 (95% CI 0.75 to 1.04) were not. Genetically predicted ALT, ALP and GGT were not clearly associated with CAD/MI (ALT OR 0.74, 95% CI 0.54 to 1.01, ALP OR 0.86, 95% CI 0.64 to 1.16 and GGT OR 1.08, 95% CI 0.97 to 1.19). We confirm observations of ALT increasing the risk of diabetes, but cannot exclude the possibility that higher ALT may protect against CAD/MI. We also cannot exclude the possibility that GGT increases the risk of CAD/MI and reduces the risk of diabetes. Informative explanations for these potentially contradictory associations should be sought. Nature Publishing Group 2016-12-20 /pmc/articles/PMC5171875/ /pubmed/27996050 http://dx.doi.org/10.1038/srep38813 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Liu, Junxi
Au Yeung, Shiu Lun
Lin, Shi Lin
Leung, Gabriel M.
Schooling, C. Mary
Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study
title Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study
title_full Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study
title_fullStr Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study
title_full_unstemmed Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study
title_short Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study
title_sort liver enzymes and risk of ischemic heart disease and type 2 diabetes mellitus: a mendelian randomization study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5171875/
https://www.ncbi.nlm.nih.gov/pubmed/27996050
http://dx.doi.org/10.1038/srep38813
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