title: Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study.
abstract: 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.
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Junxi
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Shiu Lun
authors.initials: SL
authors.lastname: Au Yeung
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Shi Lin
authors.initials: SL
authors.lastname: Lin
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Leung
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.|City University of New York Graduate School of Public Health and Health Policy, New York, NY, USA.
authors.forename: C Mary
authors.initials: CM
authors.lastname: Schooling
mesh_terms: D000410:Alanine Transaminase / Q000235:genetics / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D057182:Mendelian Randomization Analysis; D017202:Myocardial Ischemia / Q000201:enzymology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D005723:gamma-Glutamyltransferase / Q000235:genetics / Q000378:metabolism
chemical_list: D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase