Mendelian randomization estimates of alanine aminotransferase with cardiovascular disease: Guangzhou Biobank Cohort study

Hum Mol Genet. 2017 Jan 15;26(2):430-437. doi: 10.1093/hmg/ddw396.


Observational studies of the association of alanine aminotransferase (ALT) levels with ischaemic heart disease (IHD) and cardiovascular disease (CVD) risk factors are inconsistent, probably because of confounding and reverse causality. Mendelian randomization (MR) provides less confounded results. We used MR analysis to assess the associations of ALT (U/L) with IHD, diabetes and other CVD risk factors. We used instrumental variable analysis based on two single nucleotide polymorphism (SNPs) HSD17B13/MAPK10 (rs6834314) and PNPLA3/SAMM50 (rs738409) to assess the associations of ALT (U/L) with IHD, diabetes and other CVD risk factors in the Guangzhou Biobank Cohort Study (GBCS). Observationally in 19,925 participants ALT levels were strongly positively associated with self-reported IHD, systolic and diastolic blood pressure, low-density lipoprotein- and total cholesterol, triglycerides, fasting glucose, body mass index, waist circumference, heart rate (HR) and diabetes, but were not associated with uncorrected QT interval, HR-corrected QT interval or high-density lipoprotein-cholesterol. In the MR study, using a credible genetic instrument (F-statistic = 23) for ALT, ALT levels were negatively associated with IHD (odds ratio (OR) 0.92, 95% confidence interval (CI) 0.87 to 0.97) and triglycerides (β - 0.08, 95% CI - 0.13 to - 0.03), but were not associated with other CVD risk factors. Our results using Mendelian randomization suggest that ALT reduces the risk of IHD, probably through reducing triglyceride levels. The underlying mechanisms deserve further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Alanine Transaminase / genetics*
  • Biological Specimen Banks
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / pathology
  • Cohort Studies
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Lipase / genetics
  • Male
  • Membrane Proteins / genetics
  • Mendelian Randomization Analysis
  • Mitogen-Activated Protein Kinase 10
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / genetics*
  • Myocardial Ischemia / pathology
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Triglycerides / blood
  • Triglycerides / genetics


  • Membrane Proteins
  • Triglycerides
  • Alanine Transaminase
  • Mitogen-Activated Protein Kinase 10
  • Lipase
  • adiponutrin, human